KR101399409B1

KR101399409B1 - Uses of Genes as a marker for the diagnosis of lymph node metastasis of gastric cancer

Info

Publication number: KR101399409B1
Application number: KR1020120034498A
Authority: KR
Inventors: 박도윤; 전태용; 권채화
Original assignee: 부산대학교 산학협력단
Priority date: 2012-04-03
Filing date: 2012-04-03
Publication date: 2014-05-30
Also published as: KR20130112259A

Abstract

본 발명은 위암의 림프절 전이 진단 마커로서의 유전자에 관한 것으로서, 보다 상세하게는 바이오마커 유전자의 발현 수준을 측정하는 제제를 포함하는 위암의 림프절 전이 진단용 조성물; 이 조성물을 포함하는 위암의 림프절 전이 진단 키트; 위암의 림프절 전이가 의심되는 환자의 시료의 하나 이상의 마커 유전자의 발현 수준을 측정하여 그 발현 수준과 정상 대조구 시료의 해당 유전자의 발현 수준을 비교하는 것을 포함하는 위암의 림프절 전이 진단을 위한 정보 제공 방법; 및 위암의 림프절 전이의 억제 또는 예방용 물질을 스크리닝 하는 방법에 관한 것이다.The present invention relates to a gene as a marker for lymph node metastasis of gastric cancer, and more particularly, to a composition for diagnosing lymph node metastasis of gastric cancer, which comprises a preparation for measuring the expression level of a biomarker gene. A lymph node metastasis diagnostic kit for gastric cancer comprising the composition; Providing information for the diagnosis of lymph node metastasis in gastric cancer, comprising measuring the expression level of one or more marker genes of a patient suspected of having lymph node metastasis of gastric cancer and comparing the expression level thereof with the expression level of the corresponding gene in a normal control sample ; And a method for screening a substance for inhibiting or preventing lymph node metastasis of gastric cancer.

Description

위암의 림프절 전이 진단 마커로서의 유전자의 용도 {Uses of Genes as a marker for the diagnosis of lymph node metastasis of gastric cancer}BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to the use of a gene as a marker of lymph node metastasis in gastric cancer.

본 발명은 위암의 림프절 전이 여부를 외과적 시술 없이 감별할 수 있는 방법에 관한 것이다.
The present invention relates to a method for discriminating whether lymph node metastasis of gastric cancer can be performed without surgical procedure.

위암은 우리나라에서 가장 발생률이 높은 암이다. 최근 암 조기 검진사업이 시행됨에 따라 위암이 조기에 진단되는 경우가 늘고 있다. 조기위암은 림프절 전이 여부에 관계없이 위의 점막층 및 점막하층에 국한된 위암을 말하며 위암의 50%가 이 단계에서 진단되고 있다.Gastric cancer is the most common cancer in Korea. Recently, early detection of gastric cancer is increasing as the cancer screening project is implemented. Early gastric cancer is gastric cancer localized in the mucosal layer and submucosal layer regardless of lymph node metastasis. 50% of gastric cancer is diagnosed at this stage.

조기위암 중에서 림프절 전이가 없는 암은 내시경을 이용한 절제로 완치시킬 수 있지만 림프절 전이를 완벽히 예측할 수 없기 때문에 재발에 대한 염려가 있다. 따라서 위암 수술은 림프절 전이 여부가 수술 범위를 정하는 중요한 요소이다.Among early gastric cancer, cancer without lymph node metastasis can be cured by endoscopic resection, but there is concern about recurrence because lymph node metastasis can not be completely predicted. Therefore, gastric cancer surgery is an important factor for defining the scope of operation.

또한 위암 수술 후 림프절 병기 1, 2, 3인 환자의 5년간 생존율이 각각 58.1%, 23.3%, 5.9%인 반면 림프절 병기 0인 환자의 5년간 생존율이 86.1% (Zhang et al., 2004) 로 나타나 림프절 전이는 위암 환자의 예후를 결정짓는 중요한 요소이기도 하다.The 5-year survival rate of patients with stage 1, 2, and 3 stomach cancer was 58.1%, 23.3%, and 5.9%, respectively, while the survival rate of patients with lymph node 0 was 86.1% (Zhang et al., 2004) Lymph node metastasis is an important determinant of prognosis in gastric cancer patients.

위암의 수술 전 병기결정을 위해 다양한 영상방법이 사용되고 있고, 림프절 병기결정에 대해서는 34.3%~80.8%의 민감도와 75.0%~92.2%의 정확도로 다양하게 보고되고 있다 (Kwee et al., 2009). 따라서 이러한 영상방법 단독으로 위암의 림프절 전이를 결정하는 것은 어려우며, 림프절 전이를 정확히 예측할 수 있는 새로운 진단 방법이 개발되어야 할 것이다.A variety of imaging modalities have been used to determine the preoperative staging of stomach cancer, with sensitivity ranging from 34.3% to 80.8% and accuracy from 75.0% to 92.2% for lymph node staging (Kwee et al., 2009). Therefore, it is difficult to determine the lymph node metastasis in gastric cancer alone, and a new diagnostic method should be developed to accurately predict lymph node metastasis.

최근에 질병 진단을 목표로 마이크로어레이 데이터를 이용한 마커 유전자 탐색 연구가 활발히 수행되고 있으며, 특히 암과 관련된 마커 탐색에 많이 활용되고 있다.Recently, the search for marker genes using microarray data has been actively carried out in order to diagnose diseases.

위암에 대해서도 정상조직과 위암조직에서 차등 발현하는 유전자를 탐색하여 암을 진단하고 예후를 측정할 수 있는 후보 물질에 대한 보고가 많다. 하지만 림프절 전이를 진단하는 마커를 찾는 연구는 거의 없었다.There are many reports on candidates that can diagnose cancer and measure the prognosis by searching genes differentially expressed in normal tissues and gastric cancer tissues. However, few studies have looked for markers to diagnose lymph node metastasis.

한국등록특허 제 0863440호에는 위암의 전이 또는 전염 진단용 키트 및 판단 방법이 기재되어 있다.Korean Patent No. 0863440 discloses a kit for gastric cancer metastasis or infection diagnosis and a judgment method.

한국등록특허 제 0863440호Korea Patent No. 0863440

본 발명은 바이오마커 유전자의 발현수준을 측정하는 제제를 포함하는 위암의 림프절 전이 진단용 조성물, 위암의 림프절 전이 진단용 키트, 위암의 림프절 전이 진단을 위한 정보 제공 방법 및 위암 림프절 전이 차단제의 스크리닝 방법을 제공하는 것을 목적으로 한다.The present invention provides a composition for diagnosing lymph node metastasis of gastric cancer comprising a preparation for measuring the expression level of a biomarker gene, a kit for diagnosing lymph node metastasis of gastric cancer, an information providing method for diagnosing lymph node metastasis of gastric cancer, and a screening method of a gastric cancer metastatic blocker .

1. HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9로 이루어진 군에서 선택되는 하나 이상의 유전자의 발현 수준을 측정하는 제제를 포함하는 위암의 림프절 전이 진단용 조성물.The present invention relates to a method for screening for a compound of the present invention, which comprises the steps of: (1) screening for a compound of the formula (1): HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, LEC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, AMP1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, TNFRSF10A, EBP, C14orf4, TNFRSF10A, CCDF25, PTFRN, WRB, EBFB, SHBD4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, Wherein the expression level of one or more genes selected from the group consisting of KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9 is measured. Diagnostic composition.

2. 위 1에 있어서, 상기 제제는 NEU1, IPTKA, ARID3A, CKS1B, FYN, TMEM173, NRIP1, ASMTL, WDR23, 및 DCAKD로 이루어진 군에서 선택되는 하나 이상의 유전자의 발현 수준을 측정하는 것이어서 위암의 림프절 전이 병기에 대한 진단이 가능한 조성물.2. The method according to 1 above, wherein the agent is one which measures the expression level of at least one gene selected from the group consisting of NEU1, IPTKA, ARID3A, CKS1B, FYN, TMEM173, NRIP1, ASMTL, WDR23 and DCAKD, A composition capable of diagnosing cancer.

3. 위 1 또는 2에 있어서, 상기 제제는 상기 하나 이상의 유전자에 특이적으로 결합하는 프라이머, 프로브 또는 앱타머를 포함하는 것인 조성물.3. The composition of 1 or 2 above, wherein the agent comprises a primer, probe or aptamer that specifically binds to the one or more genes.

4. 위 1 또는 2의 조성물을 포함하는 위암의 림프절 전이 진단용 키트.4. A kit for the diagnosis of lymph node metastasis of gastric cancer comprising the composition of 1 or 2 above.

5. 위 4에 있어서, 마이크로어레이, RT-PCR 또는 면역분석방식에 의한 것인 키트.5. A kit as in 4 above, which is by microarray, RT-PCR or immunoassay.

6. 위암의 림프절 전이가 의심되는 환자의 시료의 HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9로 이루어진 군에서 선택되는 하나 이상의 유전자의 발현 수준을 측정하는 단계; 및6. HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4 and FAM69B in patients with suspected lymph node metastasis , SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, , MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, , RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1 , KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681 , CNOT7, HOXC4, C8or selected from the group consisting of F40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9 Determining the level of expression of one or more genes that are differentially expressed; And

상기 하나 이상의 유전자의 발현 수준을 정상 대조구 시료의 해당 유전자의 발현 수준과 비교하는 단계Comparing the expression level of said one or more genes with an expression level of a corresponding gene of a normal control sample

를 포함하는 위암의 림프절 전이 진단을 위한 정보 제공 방법.The method comprising the steps of:

7. 위 6에 있어서, 상기 정보는 위암의 림프절 전이 병기에 대한 것인 정보 제공 방법.7. The method of claim 6, wherein the information is for a lymph node metastasis stage of gastric cancer.

8. 위 6 또는 7에 있어서, 상기 하나 이상의 유전자의 발현 수준을 측정하는 단계는 마이크로어레이, 역전사효소 중합효소반응, 면역분석방식, 경쟁적 역전사효소 중합효소반응, 실시간 역전사효소 중합효소반응, RNase 보호 분석법 또는 노던 블랏팅에 의한 것인 방법.8. The method of claim 6 or 7, wherein the step of measuring the expression level of the at least one gene comprises the steps of: microarray, reverse transcriptase polymerase chain reaction, immunoassay, competitive reverse transcriptase polymerase, real-time reverse transcriptase polymerase, RNase protection &Lt; / RTI > or by Northern blotting.

9. HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9로 구성된 군으로부터 선택되는 최소 1종의 뉴클레오타이드 서열을 포함하는 세포에 분석하고자 하는 시료를 접촉시키는 단계; 및9. The method of claim 1, wherein the HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, LEC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, AMP1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, TNFRSF10A, EBP, C14orf4, TNFRSF10A, CCDF25, PTFRN, WRB, EBFB, SHBD4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, A sample to be analyzed is contacted with cells containing at least one nucleotide sequence selected from the group consisting of KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9 ; And

상기 뉴클레오티드 서열의 발현량을 측정하는 단계를 포함하는 위암의 림프절 전이의 억제 또는 예방용 물질의 스크리닝 방법.
And measuring the expression level of the nucleotide sequence.

본 발명의 위암의 림프절 전이 진단에 유용한 마커를 이용한 위암의 림프절 전이를 진단용 키트를 이용하여, 외과적 시술 없이 위암의 림프절 전이여부를 정확하고 빠르게 판별할 수 있다.Using the kit for diagnosing the lymph node metastasis of the stomach cancer using the marker useful for the diagnosis of lymph node metastasis of the present invention, it is possible to accurately and quickly discriminate the lymph node metastasis of the stomach cancer without surgery.

또한, 아직 위암이 있는 것으로 확인이 되지 않은 환자의 경우에도, 내시경 점막 절제술(endoscopic mucosal resection) 등과 같이 전이가 없는 위암에만 시술할 수 있는 치료 방법을 그 환자에게 적용하기 전에, 본 발명의 마커유전자의 발현 수준을 확인한다면 위암의 조기 치료 성적을 더욱 높일 수 있을 것이다.In addition, even in the case of patients who have not yet been confirmed to have gastric cancer, before applying a treatment method that can be performed only to gastric cancer without metastasis, such as endoscopic mucosal resection, , The early treatment of gastric cancer could be improved.

도 1은 림프절 병기 0과 1인 위암 환자와 143개 유전자의 Supervised clustering 결과를 나타낸 것이다.
도 2는 143개의 유전자의 유전자 온톨로지 결과를 나타낸 것이다.
도 3은 림프절 병기에 따른 유전자의 발현을 log2로 변환한 값이다.Figure 1 shows the results of supervised clustering of 143 genes in lymph node stage 0 and 1 stomach cancer patients.
Figure 2 shows the gene ontology results of 143 genes.
FIG. 3 shows the expression of the gene according to the lymph node stage converted to log 2.

이하 본 발명을 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail.

본 발명은 위암이 림프절로 전이된 경우가 그렇지 않은 경우에 비해 혈액에서의 본 발명의 마커인 HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6 및 CENPJ의 발현 수준이 유의적으로 증가하고, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9의 발현 수준이 유의적으로 감소한다는 점을 확인한 것에 기초한다. 즉, 본 발명에서 HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9는 위암의 림프절 전이 여부에 대한 진단 마커로 사용된다.The present invention relates to the use of the marker of the present invention in the blood as compared with the case where the gastric cancer is transplanted into the lymph node, and the marker of the present invention is the HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, SHD, FLO35776, FYN, FLO35776, FNN, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, Expression levels of BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6 and CENPJ , And increases with the increase in the amount of PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, , ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC2 5A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9. In the present invention, HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3 , ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, , FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20 , TIMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG , APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A , INTS10, PDPK1, BNIP3L, XK, C9orf 167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9 are used as diagnostic markers for lymph node metastasis in gastric cancer.

이에 따라, 본 발명은 HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9로 이루어진 군에서 선택되는 하나 이상의 유전자의 발현 수준을 측정하는 제제를 포함하는 위암의 림프절 전이 진단용 조성물을 제공한다.Accordingly, the present invention provides a method of screening for a compound of the present invention, which comprises administering to a patient a therapeutically effective amount of a compound selected from the group consisting of HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, RASAL3, LEC64675, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, RAK1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, IGF20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, VWA5A, INTS10, PDPK1, BNIP3L, XK , An agent for measuring the expression level of at least one gene selected from the group consisting of C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9 The present invention provides a composition for diagnosing lymph node metastasis of gastric cancer.

하나 이상의 상기 유전자는 위암의 림프절 전이가 의심되는 환자의 혈액 또는 조직에 포함된 것일 수 있다.One or more of the above genes may be involved in the blood or tissue of a patient suspected of having lymph node metastasis of gastric cancer.

유전자의 발현 수준을 측정하는 제제는 위암이 림프절로 전이된 경우 혈액 등의 검체에서 발현 수준이 증가되는 마커인 HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ와 발현 수준이 감소되는 마커인 PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9로 이루어진 군에서 선택되는 하나 이상의 유전자의 발현 수준을 확인함으로써 마커의 검출에 사용될 수 있는 분자를 의미한다.DRK5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, and IKKA, which are the markers that increase expression levels in specimens such as blood when gastric cancer is transplanted into lymph nodes, ARC1A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ The markers PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3 , SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, S KLK12, KLK12, KLK12, KLK12, KLK12, KLK12, KLK12, KLK12, KLK12, KLK12, KLK12, KLK12, KLK12, KLK12, KLK12, Means a molecule which can be used for the detection of a marker by confirming the expression level of one or more genes selected from the group consisting of LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9 do.

위 제제로는 바이오 키트 분야에서 통상 사용되는 것을 널리 사용할 수 있으나 예컨대 위 하나 이상의 유전자에 특이적으로 결합하는 프라이머, 프로브 또는 앱타머가 바람직하다.As the above-mentioned agents, those commonly used in the field of bio-kits can be widely used, but for example, primers, probes or aptamers which specifically bind to one or more genes are preferred.

유전자의 발현 수준은 바이오 키트 분야에서 통상 사용되는 방법에 따라 측정될 수 있는데, 예컨대 마이크로어레이, 역전사효소 중합효소반응(RT-PCR), 경쟁적 역전사효소 중합효소반응(Competitive RT-PCR), 실시간 역전사효소 중합효소반응(Real-time RT-PCR), RNase 보호 분석법(RPA; RNase protection assay), 노던 블랏팅(Northern blotting) 및 면역분석방식 등이 포함되며 이들로 제한되는 것은 아니다.The expression level of the gene can be measured according to a method commonly used in the field of a bio-kit, for example, a microarray, a reverse-transcriptase-polymerase reaction (RT-PCR), a competitive RT- But are not limited to, enzymatic polymerase chain reaction (RT-PCR), RNase protection assay (RPA), northern blotting, and immunoassay.

본 발명의 진단용 키트에서 이용되는 프로브 또는 프라이머는 HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9으로 구성된 군으로부터 선택되는 뉴클레오티드 서열에 대하여 상보적인 서열을 갖는다.The probe or primer used in the diagnostic kit of the present invention may be a probe or a primer used in a diagnostic kit such as HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, PDL2, CDR3, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC64675, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, AFP1, AMP1, AIG1, AMP1, AIP1, AMP1, AIP1, AMP2, AMP1, AMP1, AMP1, AMP2, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, C As well as the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, And a sequence complementary to a nucleotide sequence selected from the group consisting of SEQ ID NOs.

프라이머는 짧은 자유 3말단 수산화기(free 3' hydroxyl group)를 갖는 핵산 서열로 상보적인 템플레이트(template)와 염기쌍(base pair)을 형성할 수 있고 템플레이트 가닥 복사를 위한 시작 지점으로 기능을 하는 짧은 핵산 서열을 의미한다. 프라이머는 적절한 완충용액 및 온도에서 중합반응(즉, DNA 폴리머레이즈 또는 역전사효소)을 위한 시약 및 상이한 4가지 뉴클레오사이드 트리포스페이트의 존재하에서 DNA 합성이 개시될 수 있다. 본 발명에서는 위 하나 이상의 유전자에 특이적으로 결합하는 센스 및 안티센스 프라이머를 이용하여 PCR 증폭을 실시하여 발현 수준을 확인함으로써 위암의 림프절로의 전이 여부를 진단할 수 있다. PCR 조건, 센스 및 안티센스 프라이머의 길이는 당업계에 공지된 것을 기초로 변형할 수 있다.The primer is a nucleic acid sequence having a short free 3 'hydroxyl group, a short nucleic acid sequence capable of forming a base pair with a complementary template and serving as a starting point for template strand copying . Primers can be used to initiate DNA synthesis in the presence of reagents and four different nucleoside triphosphates for polymerization reactions (i. E., DNA polymerase or reverse transcriptase) at appropriate buffer solutions and temperatures. In the present invention, PCR and amplification are carried out using a sense and antisense primer specifically binding to one or more of the above genes, thereby confirming the expression level, thereby diagnosing the metastasis of the stomach cancer to the lymph node. The PCR conditions, the lengths of the sense and antisense primers can be modified based on what is known in the art.

프로브는 짧게는 수 염기 내지 길게는 수십 염기에 해당하는 RNA 또는 DNA 등의 핵산 단편을 의미하며 라벨링 되어 있다. 프로브는 올리고뉴클로타이드(oligonucleotide) 프로브, 단쇄 DNA(single stranded DNA) 프로브, 이중쇄 DNA(double stranded DNA) 프로브, RNA 프로브 등의 형태로 제작될 수 있다. 본 발명에서는 위 하나 이상의 miRNA와 상보적인 프로브를 이용하여 혼성화를 실시하여 발현 수준을 확인함으로써 위암의 림프절로의 전이 여부를 진단할 수 있다. 적당한 프로브의 선택 및 혼성화 조건은 당업계에 공지된 것을 기초로 변형할 수 있다.A probe is labeled with a nucleic acid fragment such as RNA or DNA corresponding to a short period of a few nucleotides or a long few tens of nucleotides. The probe may be prepared in the form of an oligonucleotide probe, a single stranded DNA probe, a double stranded DNA probe, or an RNA probe. In the present invention, hybridization is performed using a probe complementary to one or more of the above miRNAs to confirm the expression level, thereby diagnosing whether or not the stomach cancer is metastasized to the lymph node. Selection of suitable probes and hybridization conditions can be modified based on what is known in the art.

이러한 프라이머 또는 프로브는 공지된 HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9의 서열을 바탕으로 당업자가 적절히 디자인할 수 있다.These primers or probes may be selected from known HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1 , RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, , ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2 , IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1 , TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, , VWA5A, I Based on the sequences of NTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9 can do.

예컨대, 프라이머 또는 프로브는 포스포르아미다이트 고체 지지체 방법, 또는 기타 널리 공지된 방법을 사용하여 화학적으로 합성할 수 있다. 이러한 핵산 서열은 또한 당해 분야에 공지된 많은 수단을 이용하여 변형시킬 수 있다. 이러한 변형의 비-제한적인 예로는 메틸화, "캡화", 천연 뉴클레오타이드 하나 이상의 동족체로의 치환, 및 뉴클레오타이드 간의 변형, 예를 들면, 하전되지 않은 연결체(예: 메틸 포스포네이트, 포스포트리에스테르, 포스포로아미데이트, 카바메이트 등) 또는 하전된 연결체(예: 포스포로티오에이트, 포스포로디티오에이트 등)로의 변형이 있다.For example, primers or probes can be chemically synthesized using the phosphoramidite solid support method, or other well-known methods. Such nucleic acid sequences may also be modified using many means known in the art. Non-limiting examples of such modifications include, but are not limited to, methylation, "capping ", replacement of natural nucleotides with one or more homologues, and modifications between nucleotides, such as uncharged linkers, such as methylphosphonate, Phosphoamidates, carbamates, etc.) or charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.).

본 발명의 위암의 림프절 전이 진단용 조성물에는 위의 하나 이상의 유전자의 발현 수준을 측정하는 제제 이외에 위암의 림프절 전이 진단 키트로 사용되기에 적합하도록 하기 위한 다른 성분들이 포함될 수 있다. 예를 들어, 본 발명의 키트가 PCR 증폭 과정에 적용되는 경우에는, 본 발명의 키트는 선택적으로, PCR 증폭에 필요한 시약, 예컨대, 완충액, DNA 중합효소 (예컨대, Thermus aquaticus(Taq), Thermus thermophilus(Tth), Thermus filiformis, Thermis flavus, Thermococcus literalis 또는 Pyrococcus furiosus(Pfu)로부터 수득한 열 안정성 DNA 중합효소), DNA 중합 효소 조인자 및 dNTPs를 포함할 수 있다. 본 발명의 키트는 상기한 시약 성분을 포함하는 다수의 별도 패키징 또는 컴파트먼트로 제작될 수 있다.The composition for diagnosing the lymph node metastasis of gastric cancer of the present invention may contain other components to be suitable for use as a lymph node metastasis diagnostic kit of gastric cancer in addition to the agent for measuring the expression level of one or more of the above genes. For example, when the kit of the present invention is applied to a PCR amplification process, the kit of the present invention may optionally comprise reagents necessary for PCR amplification, such as a buffer, a DNA polymerase (e.g., Thermus aquaticus (Taq), Thermus thermophilus Thermostable DNA polymerases obtained from Thermus filiformis, Thermis flavus, Thermococcus literalis or Pyrococcus furiosus (Pfu)), DNA polymerase joins and dNTPs. The kit of the present invention may be made from a number of separate packaging or compartments containing the above reagent components.

본 발명의 진단키트는, 면역분석(immunoassay) 방식, 즉 항원-항체 반응 방식에 의한 진단키트일 수 있다. 이 경우, 상술한 본 발명의 위암 림프절 전이 마커에 특이적으로 결합하는 항체 또는 앱타머를 이용하여 실시된다.The diagnostic kit of the present invention may be an immunoassay method, that is, a diagnostic kit by an antigen-antibody reaction method. In this case, an antibody or an aptamer that specifically binds to the gastric lymph node metastasis marker of the present invention described above is used.

본 발명에서 이용되는 항체는 폴리클로날 또는 모노클로날 항체이며, 바람직하게는 모노클로날 항체이다. 항체는 당업계에서 통상적으로 실시되는 방법들, 예를 들어, 융합 방법(Kohler and Milstein, European Journal of Immunology, 6:511-519(1976)), 재조합 DNA 방법(미국 특허 제4,816,56호) 또는 파아지 항체 라이브러리 방법(Clackson et al, Nature, 352:624-628(1991) 및 Marks et al, J. Mol. Biol., 222:58, 1-597(1991))에 의해 제조될 수 있다. 항체 제조에 대한 일반적인 과정은 Harlow, E. and Lane, D., Using Antibodies: A Laboratory Manual, Cold Spring Harbor Press, New York, 1999; Zola, H., Monoclonal Antibodies: A Manual of Techniques, CRC Press, Inc., Boca Raton, Florida, 1984; 및 Coligan , CURRENT PROTOCOLS IN IMMUNOLOGY, Wiley/Greene, NY, 1991에 상세하게 기재되어 있다. 예를 들어, 단일클론 항체를 생산하는 하이브리도마 세포의 제조는 불사멸화 세포주를 항체-생산 림프구와 융합시켜 이루어지며, 이 과정에 필요한 기술은 당업자에게 잘 알려져 있으며 용이하게 실시할 수 있다. 폴리클로날 항체는 단백질 항원을 적합한 동물에게 주사하고, 이 동물로부터 항혈청을 수집한 다음, 공지의 친화성(affinity) 기술을 이용하여 항혈청으로부터 항체를 분리하여 얻을 수 있다.The antibody used in the present invention is a polyclonal or monoclonal antibody, preferably a monoclonal antibody. Antibodies can be produced using methods commonly practiced in the art, such as the fusion method (Kohler and Milstein, European Journal of Immunology, 6: 511-519 (1976)), the recombinant DNA method (US Patent No. 4,816,56) Or phage antibody library methods (Clackson et al., Nature, 352: 624-628 (1991) and Marks et al., J. Mol. Biol., 222: 58, 1-597 (1991)). General procedures for antibody preparation are described in Harlow, E. and Lane, D., Using Antibodies: A Laboratory Manual, Cold Spring Harbor Press, New York, 1999; Zola, H., Monoclonal Antibodies: A Manual of Techniques, CRC Press, Inc., Boca Raton, Florida, 1984; And Coligan, CURRENT PROTOCOLS IN IMMUNOLOGY, Wiley / Greene, NY, 1991. For example, the preparation of hybridoma cells producing monoclonal antibodies is accomplished by fusing an immortalized cell line with an antibody-producing lymphocyte, and the techniques necessary for this process are well known and readily practicable by those skilled in the art. Polyclonal antibodies can be obtained by injecting a protein antigen into a suitable animal, collecting the antiserum from the animal, and then separating the antibody from the antiserum using a known affinity technique.

면역분석 방식을 항체 또는 앱타머를 이용하여 실시하는 경우, 본 발명은 통상적인 면역분석 방법에 따라 실시하여 위암의 림프절 전이여부를 진단하는 데 이용될 수 있다.When the immunoassay is carried out using an antibody or an aptamer, the present invention can be carried out according to a conventional immunoassay to diagnose the lymph node metastasis of gastric cancer.

본 발명의 진단 키트는 유전자 칩 키트일 수 있다. 유전자 칩 키트는 유전자 또는 그의 단편에 해당하는 cDNA가 프로브로 부착되어 있는 기판, 및 형광표식 프로브를 제작하기 위한 시약, 제제, 효소 등을 포함할 수 있다. 또한, 기판은 정량 대조구 유전자 또는 그의 단편에 해당하는 cDNA를 포함할 수 있다.The diagnostic kit of the present invention may be a gene chip kit. The gene chip kit may include a substrate on which a cDNA corresponding to a gene or a fragment thereof is attached as a probe, and reagents, preparations, enzymes, and the like for producing a fluorescent-labeled probe. In addition, the substrate may contain a cDNA corresponding to a quantitative control gene or a fragment thereof.

본 발명의 다른 일 구현 예로서, 본 발명은 위암의 림프절 전이가 의심되는 환자의 시료의 HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9로 이루어진 군에서 선택되는 하나 이상의 miRNA의 발현 수준을 측정하는 단계; 및 위 하나 이상의 유전자의 발현 수준을 정상 대조구 시료의 해당 유전자의 발현 수준과 비교하는 단계를 포함하는 위암의 림프절 전이 진단을 위한 정보 제공 방법에 관한 것이다.In another embodiment of the present invention, the present invention provides a method for screening a sample of a patient suspected of having lymph node metastasis of gastric cancer, comprising the steps of: (a) contacting a sample of a patient suspected of having lymph node metastasis of gastric cancer with HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, , C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP , SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650 , BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP , C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2 , DCAKD, LOC14 ARSD, TRIM29, CCDC58, CTC58, CTC58, CTL7, CTNNBl, ARSD, TRIM29, Determining the level of expression of one or more miRNAs selected from the group consisting of DEFBl, FAM3D, GABRP, and CA9; And comparing the expression level of the at least one gene with the level of expression of the corresponding gene in a normal control sample, to a method for providing information for diagnosis of lymph node metastasis of gastric cancer.

즉, 시료에서 본 발명의 마커인 HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6 및 CENPJ로 구성된 군으로부터 선택되는 1종이상의 뉴클레오티드 서열에 대한 혼성화 시그널이 정상시료(예컨대, 정상 위 상피세포)보다 강하게 나오거나, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9로 구성된 군으로부터 선택되는 1종 이상의 뉴클레오티드 서열에 대한 혼성화 시그널이 정상시료(예컨대, 정상 위 상피세포)보다 약하게 나오는 경우에는 위암이 림프절로 전이되었다는 정보를 제공할 수 있게 된다.In the sample, the marker of the present invention, HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A , KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96 A hybridization signal for one or more nucleotide sequences selected from the group consisting of GRT1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, and CENPJ, Or normal stomach epithelium) or may be more strongly expressed by PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, , SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, AS MTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, A hybridization signal for at least one nucleotide sequence selected from the group consisting of XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9 If it is weaker than the normal sample (for example, normal stomach epithelial cells), it can provide information that the stomach cancer has transferred to the lymph node.

본 발명에서 하나 이상의 유전자의 발현 수준을 측정하는 단계는 위에서 이미 설명한 바와 같이 마이크로어레이, 역전사효소 중합효소반응, 경쟁적 역전사효소 중합효소반응, 실시간 역전사효소 중합효소반응, RNase 보호 분석법 또는 노던 블랏팅에 의해 수행될 수 있다.In the present invention, the step of measuring the expression level of one or more genes may be carried out by a microarray, a reverse transcriptase polymerase, a competitive reverse transcriptase polymerase, a real-time reverse transcriptase polymerase, an RNase protection assay or a Northern blotting &Lt; / RTI >

본 발명의 다른 일 구현 예로서, 본 발명은 다음의 단계를 포함하는 위암의 림프절 전이의 억제 또는 예방용 물질의 스크리닝 방법을 제공한다:In another embodiment of the present invention, the present invention provides a method of screening a substance for inhibiting or preventing lymph node metastasis of gastric cancer comprising the steps of:

(a) HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9로 구성된 군으로부터 선택되는 최소 1종의 뉴클레오타이드 서열을 포함하는 세포에 분석하고자 하는 시료를 접촉시키는 단계; 및(a) HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1 , FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1 , TMEC156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6, CENPJ, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173 , SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2 , IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10 , PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, A sample to be analyzed is contacted with cells containing at least one nucleotide sequence selected from the group consisting of KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9 ; And

(b) 상기 뉴클레오티드 서열의 발현량을 측정하는 단계, HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, CENPN, ARHGAP4, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6 및 CENPJ로 구성된 군으로부터 선택되는 1종 이상의 뉴클레오티드 서열에 대한 혼성화 시그널의 과별현이 억제되거나, PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, MIPOL1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C21orf33, WDR23, TKT, SAV1, TMEM106B, SLC25A6, FUT6, LOC402251, DKFZp761P0423, NEIL2, ICAM2, DCAKD, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9orf167, PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9로 구성된 군으로부터 선택되는 1종 이상의 뉴클레오티드 서열에 대한 혼성화 시그널의 저발현이 억제되는 경우에는 상기 시료는 위암의 림프절 전이의 억제 또는 예방용 물질로 판정된다.(b) measuring the expression level of the nucleotide sequence; measuring the expression level of the nucleotide sequence; and determining the expression level of the nucleotide sequence of the HLA-DRB5, DACH1, IRX3, NEU1, CD7, YBX2, HOXA11AS, ITPKA, MICB, ENO3, ARID3A, LTB, NINJ2, C20orf100, NES, FAM69B, SLC27A3, EFCAB4A, KIFC1, RASAL3, ABCB1, FOXA3, TEAD4, CKS1B, SLC39A8, TNC, ELOVL5, LOC730102, SLC26A6, AURKA, ICAM3, LOC729086, FYN, FLJ35776, SHD, BRI3BP, SLC37A4, INPP5E, HIST1H4H, GTF3A, A hybridization signal for at least one nucleotide sequence selected from the group consisting of C13orf23, MLH1, CD96, GRTP1, ETS1, FOXM1, TMEM156, EXOSC8, ZC3H3, LOC646753, ESPN, FLOT1, DTNA, SPTBN5, KBTBD12, VARS2, CD6 and CENPJ Or alternatively PIGP, LOC440595, LOC653650, BSPRY, ALDH6A1, MRPL43, C11orf74, PDCD2, RAC1, PCM1, HEPACAM2, IFT20, TMEM173, SH2D4A, ERLIN2, NXF3, ABTB1, MCPH1, TNFRSF10B, PCBD1, SDC1, EXTL3, AMP1, AIG1, KCNK1, UBXN8, NRIP1, TFG, APPBP2, IFT74, DSG2, ASMTL, TMEM66, C2, SLC38A10, ZNF395, C17orf58, PTGFRN, WRB, EBP, C14orf4, TNFRSF10A, CCDC25, LOC148430, LOC651149, PPP2R2A, FLJ43681, CNOT7, HOXC4, C8orf40, VWA5A, INTS10, PDPK1, BNIP3L, XK, C9OF167, SOC254, The low expression of the hybridization signal for one or more nucleotide sequences selected from the group consisting of PROSC, DDIT4, KLK12, LOC339352, FDFT1, GSTO2, ZNF185, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9 If inhibited, the sample is judged to be a substance for inhibiting or preventing lymph node metastasis of gastric cancer.

본 발명의 방법에 따르면, 우선 본 발명의 마커의 뉴클레오티드 서열을 포함하는 세포에 분석하고자 하는 시료를 접촉시킨다. 바람직하게는, 본 발명의 마커의 뉴클레오티드 서열을 포함하는 세포는 인간의 위암 세포이다. 본 발명의 스크리닝 방법을 언급하면서 사용되는 용어 “시료”는 본 발명의 마커의 발현량에 영향을 미치는지 여부를 검사하기 위하여 스크리닝에서 이용되는 미지의 물질을 의미한다. 상기 시료는 화학물질, 뉴클레오타이드, 안티센스-RNA, siRNA(small interference RNA) 및 천연물 추출물을 포함하나, 이에 한정되는 것은 아니다.According to the method of the present invention, first, the sample to be analyzed is brought into contact with the cells containing the nucleotide sequence of the marker of the present invention. Preferably, the cell comprising the nucleotide sequence of the marker of the invention is a human gastric cancer cell. The term " sample " used in referring to the screening method of the present invention means an unknown substance used in screening to check whether the expression level of the marker of the present invention is affected. Such samples include, but are not limited to, chemicals, nucleotides, antisense-RNA, siRNA (small interference RNA) and natural extracts.

이어, 시료가 처리된 세포에서 본 발명의 마커의 발현량을 측정한다. 발현량의 측정은 상기 기재한 바와 같이 실시할 수 있으며, 측정 결과, 본 발명의 마커의 뉴클레오티드 서열의 고발현 또는 저발현이 억제되는 경우에는 상기 시료는 위암의 림프절 전이의 억제 또는 예방용 물질로 판정될 수 있다.Next, the expression level of the marker of the present invention is measured in the sample-treated cells. Measurement of the expression level can be carried out as described above. As a result of the measurement, when the high expression or low expression of the nucleotide sequence of the marker of the present invention is inhibited, the sample is used as a substance for inhibiting or preventing the lymph node metastasis Can be determined.

본 발명의 다른 일 구현 예로서, 본 발명은 위암의 림프절 전이가 이미 일어난 경우, 림프절 병기 단계를 구별할 수 있는 진단 또는 예후 분석용 키트, 진단을 위한 정보제공방법 및 억제제 스크리닝 방법을 제공한다. 상기 기재한 위암의 림프절 전이의 진단 또는 예후 분석용 키트, 진단을 위한 정보제공방법 및 억제제 스크리닝 방법의 경우와 동일하게 적용가능하다.As another embodiment of the present invention, the present invention provides a diagnostic or prognostic kit for distinguishing lymph node metastasis when lymph node metastasis has already occurred in stomach cancer, information providing method for diagnosis, and screening method of inhibitor. The present invention is applicable to the kit for analyzing the diagnosis or prognosis of the lymph node metastasis of gastric cancer described above, the information providing method for diagnosis, and the screening method for inhibitor.

NEU1, IPTKA, ARID3A, CKS1B 및 FYN로 이루어진 군의 뉴클레오티드 서열에 대한 혼성화 시그널이 정상시료보다 강하게 나오거나, TMEM173, NRIP1, ASMTL, WDR23 및 DCAKD로 이루어진 군의 뉴클레오티드 서열에 대한 혼성화 시그널이 정상시료보다 약하게 나오는 경우, 위암의 림프절 병기 단계가 높은 경우에 해당한다는 정보를 제공할 수 있다. 상기 유전자군에 대한 시그널은 림프절 전이가 없는 위암조직(N0)과는 구별되면서 림프절 병기(N1, N2, N3)에 따라 차이를 보인다.The hybridization signal for the nucleotide sequence of the group consisting of NEU1, IPTKA, ARID3A, CKS1B and FYN is stronger than the normal sample or the hybridization signal for the nucleotide sequence of the group consisting of TMEM173, NRIP1, ASMTL, WDR23 and DCAKD is higher than that of the normal sample If it is weak, it can provide information that the lymph node stage of gastric cancer is high. The signal for the gene group differs according to the lymph node stage (N1, N2, N3) while being differentiated from the gastric cancer tissue (N0) without lymph node metastasis.

이하, 본 발명을 구체적으로 설명하기 위해 실시예를 들어 상세하게 설명하기로 한다.
BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to examples.

실시예Example 1. 위암 환자의 조직으로부터 1. From the tissue of gastric cancer patient 마이크로어레이Microarray 수행을 통한 림프절 전이에 따라 차등 발현되는 143개의 유전자 확인 Identification of 143 genes that are differentially expressed according to lymph node metastasis through performance

부산대학교병원(PNU)과 전남대학교화순병원(JNU)으로부터 T 병기가 2와 3인 33명의 위암 환자의 조직을 분양받아 RNA를 추출하여 마이크로어레이를 수행하였다. 그 결과 얻은 gene expression profiling data를 normalization하여 이 후 분석에 사용되었다. 표1은 실험에 사용한 33명 위암환자의 임상정보이다.The tissues of 33 stomach cancer patients with T stage 2 and 3 were obtained from PNU and Chonnam National University Hwasun Hospital (JNU) and RNA was extracted and microarray was performed. The resulting gene expression profiling data was normalized and used for subsequent analysis. Table 1 shows the clinical data of 33 patients with gastric cancer.

구분division PNU (n=18)PNU (n = 18) JNU (n=15)JNU (n = 15) 나이age 65세이하Under 65 88 1111 65세초과Greater than 65 years 1010 44 성별gender 남south 1212 1414 녀Girl 66 1One 조직학적타입Histological type IntestinalIntestinal 1414 1414 DiffuseDiffuse 44 00 MixedMixed 00 1One T병기T armor T2T2 33 66 T3T3 1515 99 N병기N armory N0N0 33 55 N1N1 33 66 N2N2 66 44 N3N3 66 00

먼저 림프절 전이가 없는 환자군(N0)과 림프절 전이 병기 1(N1)인 환자군에서 유의수준 (p<0.05, fold change>1.5)으로 차등 발현되는 143개의 유전자군을 찾았다. 림프절 전이가 없는 환자군에 비해 림프절 병기 1인 환자군에서 증가하는 유전자가 60개(표 2 참조), 감소하는 유전자가 83개(표 3 참조)였다.First, we found 143 genes that were differentially expressed at a significant level (p <0.05, fold change> 1.5) in patients with no lymph node metastasis (N0) and those with lymph node metastasis stage 1 (N1). There were 60 genes (see Table 2) and 83 genes (see Table 3) that increased in the lymph node stage 1 patient group compared to the non-lymph node metastasis group.

전체적으로 대조군과 비교하여 2배 이상 발현 변화를 보이는 것은 반응 증가에서는 6개의 유전자(HLA-DRB5, DACH1, IRX3, NEU1, CD7 및 YBX2) 및 반응 감소에서는 14개의 유전자(LOC339352, FDFT1, GSTO2, ZNF185, FDFT1, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP 및 CA9)를 확인할 수 있었다.(LOC339352, FDFT1, GSTO2, ZNF185, and GSTO2) in response to 6 genes (HLA-DRB5, DACH1, IRX3, NEU1, CD7 and YBX2) FDFT1, SOX7, CTNNB1, ARSD, TRIM29, CCDC58, DEFB1, FAM3D, GABRP and CA9).

특히 HLA-DRB5는 발현이 6.91배 증가되었으며, CA9는 발현이 4.94배 감소하였다. In particular, expression of HLA-DRB5 was increased 6.91-fold and expression of CA9 was decreased 4.94-fold.

143개 유전자와 환자에 대해 hierarchical clustering을 수행결과, 림프절 전이가 없는 환자군과 림프절 전이 병기 1인 환자군이 명확하게 차이나는 두 개의 군으로 clustering되는 것을 알 수 있다(도 1 참조). 이것은 143개의 유전자가 NO와 N1을 잘 구분할 수 있다는 것을 제시한다.
As a result of hierarchical clustering of 143 genes and patients, it can be seen that the patient group without lymph node metastasis and the patient group with lymph node metastasis were clustering into two distinct groups (see FIG. 1). This suggests that 143 genes can distinguish between NO and N1.

발현증가Increased expression PROBE_IDPROBE_ID GENE
SYMBOLGENE
SYMBOL GENE TITLEGENE TITLE p-valuep-value fold
changefold
change ILMN_1697499ILMN_1697499 HLA-DRB5HLA-DRB5 major histocompatibility complex, class II, DR beta 5major histocompatibility complex, class II, DR beta 5 0.04 0.04 6.91 6.91 ILMN_1755741ILMN_1755741 DACH1DACH1 dachshund homolog 1 (Drosophila)dachshund homolog 1 (Drosophila) 0.04 0.04 2.97 2.97 ILMN_1811468ILMN_1811468 IRX3IRX3 iroquois homeobox 3iroquois homeobox 3 0.01 0.01 2.54 2.54 ILMN_1763144ILMN_1763144 NEU1NEU1 sialidase 1 (lysosomal sialidase)sialidase 1 (lysosomal sialidase) 0.01 0.01 2.28 2.28 ILMN_1792538ILMN_1792538 CD7CD7 CD7 antigen (p41); T-cell antigen CD7CD7 antigen (p41); T-cell antigen CD7 0.02 0.02 2.22 2.22 ILMN_1755354ILMN_1755354 YBX2YBX2 Yboxbindingprotein2 Yboxbindingprotein2 0.04 0.04 2.02 2.02 ILMN_3249281ILMN_3249281 HOXA11ASHOXA11AS HOXA11 antisense RNA (non-protein coding)HOXA11 antisense RNA (non-protein coding) 0.04 0.04 1.94 1.94 ILMN_1776516ILMN_1776516 ITPKAITPKA inositol-trisphosphate 3-kinase Ainositol-trisphosphate 3-kinase A 0.05 0.05 1.91 1.91 ILMN_1708006ILMN_1708006 MICBMICB MHC class I polypeptide-related sequence BMHC class I polypeptide-related sequence B 0.02 0.02 1.90 1.90 ILMN_1678904ILMN_1678904 ENO3ENO3 enolase3,betamuscle enolase3, betamuscle 0.03 0.03 1.89 1.89 ILMN_1670130ILMN_1670130 ARID3AARID3A ATrichinteractivedomain3A(BRIGHT-like) ATrichinteractivedomain3A (BRIGHT-like) 0.02 0.02 1.89 1.89 ILMN_2376205ILMN_2376205 LTBLTB lymphotoxinbeta(TNFsuperfamily,member3) lymphotoxinbeta (TNFsuperfamily, member3) 0.03 0.03 1.86 1.86 ILMN_1731745ILMN_1731745 NINJ2NINJ2 ninjurin2 ninjurin2 0.01 0.01 1.81 1.81 ILMN_2082209ILMN_2082209 C20orf100C20orf100 TOX high mobility group box family member 2TOX high mobility group box family member 2 0.02 0.02 1.81 1.81 ILMN_1738147ILMN_1738147 NESNES nestinnestin 0.02 0.02 1.80 1.80 ILMN_1720526ILMN_1720526 CENPNCENPN centromere protein Ncentromere protein N 0.00 0.00 1.79 1.79 ILMN_1770824ILMN_1770824 ARHGAP4ARHGAP4 RhoGTPaseactivatingprotein4 RhoGTPaseactivating protein 4 0.02 0.02 1.78 1.78 ILMN_1757440ILMN_1757440 FAM69BFAM69B family with sequence similarity 69, member Bfamily with sequence similarity 69, member B 0.05 0.05 1.77 1.77 ILMN_1719627ILMN_1719627 SLC27A3SLC27A3 solute carrier family 27 (fatty acid transporter), member 3solute carrier family 27 (fatty acid transporter), member 3 0.01 0.01 1.76 1.76 ILMN_1745623ILMN_1745623 EFCAB4AEFCAB4A EF-hand calcium binding domain 4AEF-hand calcium binding domain 4A 0.01 0.01 1.76 1.76 ILMN_2222008ILMN_2222008 KIFC1KIFC1 kinesinfamilymemberC1 kinesinfamilymemberC1 0.03 0.03 1.74 1.74 ILMN_1795089ILMN_1795089 RASAL3RASAL3 RAS protein activator like 3RAS protein activator like 3 0.01 0.01 1.74 1.74 ILMN_1812070ILMN_1812070 ABCB1ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), member 1ATP-binding cassette, sub-family B (MDR / TAP), member 1 0.04 0.04 1.70 1.70 ILMN_1792733ILMN_1792733 FOXA3FOXA3 forkheadboxA3 forkheadboxA3 0.05 0.05 1.69 1.69 ILMN_1705301ILMN_1705301 TEAD4TEAD4 TEA domain family member 4TEA domain family member 4 0.02 0.02 1.68 1.68 ILMN_2041046ILMN_2041046 CKS1BCKS1B CDC28 protein kinase regulatory subunit 1BCDC28 protein kinase regulatory subunit 1B 0.01 0.01 1.68 1.68 ILMN_1695316ILMN_1695316 SLC39A8SLC39A8 solute carrier family 39 (metal ion transporter), member 8solute carrier family 39 (metal ion transporter), member 8 0.00 0.00 1.67 1.67 ILMN_2145670ILMN_2145670 TNCTNC tenascin Ctenascin C 0.05 0.05 1.66 1.66 ILMN_2174369ILMN_2174369 ELOVL5ELOVL5 ELOVL fatty acid elongase 5ELOVL fatty acid elongase 5 0.03 0.03 1.66 1.66 ILMN_3306801ILMN_3306801 LOC730102LOC730102 quinone oxidoreductase-like protein 2 pseudogenequinone oxidoreductase-like protein 2 pseudogene 0.02 0.02 1.65 1.65 ILMN_1785252ILMN_1785252 SLC26A6SLC26A6 solute carrier family 26, member 6solute carrier family 26, member 6 0.02 0.02 1.65 1.65 ILMN_2357438ILMN_2357438 AURKAAURKA aurora kinase Aaurora kinasea 0.01 0.01 1.65 1.65 ILMN_2212763ILMN_2212763 ICAM3ICAM3 intercellularadhesionmolecule3 intercellularadhesionmolecule3 0.00 0.00 1.65 1.65 ILMN_3230435ILMN_3230435 LOC729086LOC729086 vesicular, overexpressed in cancer, prosurvival protein 1 pseudogenevesicular, overexpressed in cancer, prosurvival protein 1 pseudogene 0.05 0.05 1.64 1.64 ILMN_1686555ILMN_1686555 FYNFYN FYNoncogenerelatedtoSRC,FGR,YES FYNoncogenerelatedtoSRC, FGR, YES 0.01 0.01 1.63 1.63 ILMN_3307940ILMN_3307940 FLJ35776FLJ35776 uncharacterizedLOC649446 uncharacterizedLOC649446 0.02 0.02 1.63 1.63 ILMN_1789166ILMN_1789166 SHDSHD src homology 2 domain-containing transforming protein Dsrc homology 2 domain-containing transforming protein D 0.02 0.02 1.63 1.63 ILMN_1797693ILMN_1797693 BRI3BPBRI3BP BRI3bindingprotein BRI3 binding protein 0.02 0.02 1.63 1.63 ILMN_1678678ILMN_1678678 SLC37A4SLC37A4 solute carrier family 37 (glucose-6-phosphate transporter), member 4solute carrier family 37 (glucose-6-phosphate transporter), member 4 0.03 0.03 1.61 1.61 ILMN_1811301ILMN_1811301 INPP5EINPP5E inositolpolyphosphate-5-phosphatase,72kDa inositolpolyphosphate-5-phosphatase, 72 kDa 0.01 0.01 1.61 1.61 ILMN_1751120ILMN_1751120 HIST1H4HHIST1H4H histonecluster1,H4h histoneCluster1, H4h 0.01 0.01 1.60 1.60 ILMN_1658464ILMN_1658464 GTF3AGTF3A generaltranscriptionfactorIIIA generaltranscriptionfactorIIIA 0.02 0.02 1.59 1.59 ILMN_1795128ILMN_1795128 C13orf23C13orf23 prolineandserinerich1 prolineandserinerich1 0.03 0.03 1.59 1.59 ILMN_1788363ILMN_1788363 MLH1MLH1 mutLhomolog1,coloncancer,nonpolyposistype2(E.coli) mutLhomolog1, coloncancer, nonpolyposistype2 (E. coli) 0.05 0.05 1.58 1.58 ILMN_2415786ILMN_2415786 CD96CD96 CD96antigen;Tcellactivation,increasedlateexpression;T-cellsurfaceproteintactile;cellsurfaceantigenCD96;tcell-activatedincreasedlateexpressionproteinCD96antigen; Tcellactivation; IncreaseLateExpression; T-CellSurface ProteinTactile; CellSurfaceAntigenCD96; Tcell-ActivatedCreasedLateExpression Protein 0.05 0.05 1.58 1.58 ILMN_2142353ILMN_2142353 GRTP1GRTP1 GH regulated TBC protein 1GH regulated TBC protein 1 0.03 0.03 1.57 1.57 ILMN_2122103ILMN_2122103 ETS1ETS1 v-etserythroblastosisvirusE26oncogenehomolog1(avian) v-etserythroblastosisvirusE26oncogenehomolog1 (avian) 0.02 0.02 1.56 1.56 ILMN_2391551ILMN_2391551 C13orf23C13orf23 prolineandserinerich1 prolineandserinerich1 0.05 0.05 1.55 1.55 ILMN_2344971ILMN_2344971 FOXM1FOXM1 forkheadboxM1 forkheadboxM1 0.02 0.02 1.55 1.55 ILMN_2095660ILMN_2095660 TMEM156TMEM156 transmembraneprotein156 transmembraneoprotein156 0.04 0.04 1.54 1.54 ILMN_1756162ILMN_1756162 EXOSC8EXOSC8 exosome component 8exosome component 8 0.01 0.01 1.53 1.53 ILMN_1680955ILMN_1680955 AURKAAURKA aurorakinaseA aurorakinaseA 0.01 0.01 1.53 1.53 ILMN_1702389ILMN_1702389 ZC3H3ZC3H3 CG6694geneproductfromtranscriptCG6694-RA CG6694geneproductfromtranscriptCG6694-RA 0.02 0.02 1.53 1.53 ILMN_3290019ILMN_3290019 LOC646753LOC646753 ribosomalproteinS26pseudogene2 ribosomalproteinS26pseudogene2 0.04 0.04 1.53 1.53 ILMN_1806710ILMN_1806710 ESPNESPN espin espin 0.02 0.02 1.53 1.53 ILMN_1719256ILMN_1719256 CKS1BCKS1B CDC28proteinkinaseregulatorysubunit1B CDC28proteinkinaseregulatorysubunit1B 0.01 0.01 1.52 1.52 ILMN_1661439ILMN_1661439 FLOT1FLOT1 flotillin1 flotillin1 0.02 0.02 1.52 1.52 ILMN_1730201ILMN_1730201 DTNADTNA dystrobrevin,alpha dystrobrevin, alpha 0.04 0.04 1.52 1.52 ILMN_1807609ILMN_1807609 SPTBN5SPTBN5 spectrin, beta, non-erythrocytic 5spectrin, beta, non-erythrocytic 5 0.03 0.03 1.52 1.52 ILMN_1713523ILMN_1713523 KBTBD12KBTBD12 kelch repeat and BTB (POZ) domain containing 12kelch repeat and BTB (POZ) domain containing 12 0.04 0.04 1.51 1.51 ILMN_1737585ILMN_1737585 VARS2VARS2 valyl-tRNA synthetase 2, mitochondrial (putative)valyl-tRNA synthetase 2, mitochondrial (putative) 0.03 0.03 1.50 1.50 ILMN_2380801ILMN_2380801 FYNFYN FYNoncogenerelatedtoSRC,FGR,YES FYNoncogenerelatedtoSRC, FGR, YES 0.00 0.00 1.50 1.50 ILMN_1746565ILMN_1746565 CD6CD6 CD6 antigen; T-cell differentiation antigen CD6; T12CD6 antigen; T-cell differentiation antigen CD6; T12 0.02 0.02 1.50 1.50 ILMN_1661776ILMN_1661776 CENPJCENPJ centromereproteinJ centromereproteinJ 0.01 0.01 1.50 1.50

발현감소Decreased expression PROBE_IDPROBE_ID GENE
SYMBOLGENE
SYMBOL GENE TITLEGENE TITLE p-valuep-value fold
changefold
change ILMN_1774949ILMN_1774949 PIGPPIGP phosphatidylinositol glycan anchor biosynthesis, class Pphosphatidylinositol glycan anchor biosynthesis, class P 0.02 0.02 -1.50 -1.50 ILMN_3218248ILMN_3218248 LOC440595LOC440595 eukaryotictranslationelongationfactor1alpha1pseudogene11 eukaryotictranslationelongationfactor1alpha1pseudogene11 0.04 0.04 -1.50 -1.50 ILMN_1683903ILMN_1683903 LOC653650LOC653650 3-phosphoinositide dependent protein kinase 1 pseudogene3-phosphoinositide dependent protein kinase 1 pseudogene 0.04 0.04 -1.50 -1.50 ILMN_3247560ILMN_3247560 BSPRYBSPRY B-boxandSPRYdomaincontaining B-boxandSPRYdomaincontaining 0.04 0.04 -1.50 -1.50 ILMN_1785284ILMN_1785284 ALDH6A1ALDH6A1 aldehydedehydrogenase6family,memberA1 aldehydedehydrogenase6family, memberA1 0.02 0.02 -1.51 -1.51 ILMN_1700477ILMN_1700477 MRPL43MRPL43 mitochondrial ribosomal protein L43mitochondrial ribosomal protein L43 0.04 0.04 -1.51 -1.51 ILMN_1659017ILMN_1659017 C11orf74C11orf74 chromosome11openreadingframe74 chromosome11openreadingframe74 0.03 0.03 -1.51 -1.51 ILMN_1797684ILMN_1797684 PDCD2PDCD2 programmed cell death 2programmed cell death 2 0.03 0.03 -1.51 -1.51 ILMN_1652445ILMN_1652445 RAC1RAC1 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) 0.05 0.05 -1.52 -1.52 ILMN_2042595ILMN_2042595 PCM1PCM1 pericentriolarmaterial1 pericentriolarmaterial1 0.04 0.04 -1.52 -1.52 ILMN_2388263ILMN_2388263 HEPACAM2HEPACAM2 HEPACAMfamilymember2 HEPACAMfamilymember2 0.05 0.05 -1.53 -1.53 ILMN_3235216ILMN_3235216 IFT20IFT20 intraflagellar transport 20 homolog (Chlamydomonas)intraflagellar transport 20 homolog (Chlamydomonas) 0.04 0.04 -1.53 -1.53 ILMN_2145116ILMN_2145116 TMEM173TMEM173 transmembraneprotein173 transmembrane protein 173 0.05 0.05 -1.53 -1.53 ILMN_1679322ILMN_1679322 SH2D4ASH2D4A SH2domaincontaining4A SH2domaincontaining4A 0.03 0.03 -1.53 -1.53 ILMN_1700549ILMN_1700549 ERLIN2ERLIN2 ER lipid raft associated 2ER lipid raft associated 2 0.04 0.04 -1.53 -1.53 ILMN_1674343ILMN_1674343 NXF3NXF3 nuclear RNA export factor 3nuclear RNA export factor 3 0.03 0.03 -1.54 -1.54 ILMN_2367165ILMN_2367165 ABTB1ABTB1 ankyrin repeat and BTB (POZ) domain containing 1ankyrin repeat and BTB (POZ) domain containing 1 0.01 0.01 -1.54 -1.54 ILMN_1753122ILMN_1753122 MCPH1MCPH1 microcephalin 1microcephalin 1 0.01 0.01 -1.54 -1.54 ILMN_1699265ILMN_1699265 TNFRSF10BTNFRSF10B tumornecrosisfactorreceptorsuperfamily,member10b tumornecrosisfactorreceptorsuperfamily, member10b 0.03 0.03 -1.54 -1.54 ILMN_1813456ILMN_1813456 PCBD1PCBD1 pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alphapterin-4 alpha-carbinolamine dehydratase / dimerization cofactor of hepatocyte nuclear factor 1 alpha 0.03 0.03 -1.54 -1.54 ILMN_1815308ILMN_1815308 SDC1SDC1 syndecan 1syndecan 1 0.05 0.05 -1.54 -1.54 ILMN_1778226ILMN_1778226 EXTL3EXTL3 exostoses (multiple)-like 3exostoses (multiple) -like 3 0.00 0.00 -1.55 -1.55 ILMN_2277419ILMN_2277419 SLC38A10SLC38A10 solutecarrierfamily38,member10 solutecarrierfamily38, member10 0.00 0.00 -1.55 -1.55 ILMN_1772876ILMN_1772876 ZNF395ZNF395 zincfingerprotein395 zincfingerprotein395 0.03 0.03 -1.55 -1.55 ILMN_1712985ILMN_1712985 C17orf58C17 O58 chromosome17openreadingframe58 chromosome17openreadingframe58 0.04 0.04 -1.55 -1.55 ILMN_1743130ILMN_1743130 PTGFRNPTGFRN prostaglandinF2receptornegativeregulator prostaglandinF2receptornegativeregulator 0.01 0.01 -1.56 -1.56 ILMN_2096985ILMN_2096985 ALDH6A1ALDH6A1 aldehydedehydrogenase6family,memberA1 aldehydedehydrogenase6family, memberA1 0.02 0.02 -1.56 -1.56 ILMN_1695092ILMN_1695092 WRBWRB tryptophanrichbasicprotein tryptophanrichbasicprotein 0.03 0.03 -1.56 -1.56 ILMN_2073604ILMN_2073604 EBPEBP emopamil binding protein (sterol isomerase)emopamil binding protein (sterol isomerase) 0.04 0.04 -1.56 -1.56 ILMN_1804396ILMN_1804396 C14orf4C14Fr4 interferon regulatory factor 2 binding protein-likeinterferon regulatory factor 2 binding protein-like 0.03 0.03 -1.57 -1.57 ILMN_1721316ILMN_1721316 TNFRSF10ATNFRSF10A tumornecrosisfactorreceptorsuperfamily,member10a tumornecrosisfactorreceptorsuperfamily, member10a 0.02 0.02 -1.57 -1.57 ILMN_1789266ILMN_1789266 CCDC25CCDC25 coiled-coildomaincontaining25 coiled-coildomaincontaining25 0.04 0.04 -1.57 -1.57 ILMN_3307654ILMN_3307654 MIPOL1MIPOL1 MIPOL1MIPOL1 0.00 0.00 -1.57 -1.57 ILMN_1797974ILMN_1797974 AIG1AIG1 androgen-induced1 androgen-induced1 0.01 0.01 -1.58 -1.58 ILMN_1718863ILMN_1718863 KCNK1KCNK1 potassiumchannel,subfamilyK,member1 potassiumchannel, subfamilyK, member1 0.05 0.05 -1.58 -1.58 ILMN_1731891ILMN_1731891 UBXN8UBXN8 UBX domain protein 8UBX domain protein 8 0.02 0.02 -1.58 -1.58 ILMN_1718629ILMN_1718629 NRIP1NRIP1 nuclear receptor interacting protein 1nuclear receptor interacting protein 1 0.00 0.00 -1.59 -1.59 ILMN_2341815ILMN_2341815 TFGTFG TRK-fusedgene TRK-fusedgene 0.03 0.03 -1.59 -1.59 ILMN_2149766ILMN_2149766 APPBP2APPBP2 amyloid beta precursor protein (cytoplasmic tail) binding protein 2amyloid beta precursor protein (cytoplasmic tail) binding protein 2 0.02 0.02 -1.59 -1.59 ILMN_1777449ILMN_1777449 IFT74IFT74 intraflagellartransport74homolog(Chlamydomonas) intraflagellartransport74homolog (Chlamydomonas) 0.05 0.05 -1.60 -1.60 ILMN_1704196ILMN_1704196 DSG2DSG2 desmoglein 2desmoglein 2 0.04 0.04 -1.60 -1.60 ILMN_1804384ILMN_1804384 ASMTLASMTL acetylserotoninO-methyltransferase-like acetylserotoninO-methyltransferase-like 0.02 0.02 -1.61 -1.61 ILMN_1780141ILMN_1780141 TMEM66TMEM66 transmembraneprotein66 transmembraneoprotein66 0.05 0.05 -1.61 -1.61 ILMN_2386205ILMN_2386205 C21orf33C21orf33 chromosome21openreadingframe33;ES1proteinhomolog,mitochondrial;KeionovelproteinI;humanHES1protein,homologtoE.coliandzebrafishES1proteinchromosome21openreadingframe33; ES1proteinhomolog, mitochondrial; KeionovelproteinI; humanHES1protein, homologtoE.coliandzebrafishES1protein 0.00 0.00 -1.61 -1.61 ILMN_1765825ILMN_1765825 WDR23WDR23 WD40repeat-containingprotein WD40repeat-containingprotein 0.02 0.02 -1.62 -1.62 ILMN_1736597ILMN_1736597 TKTTKT transketolasetransketolase 0.03 0.03 -1.62 -1.62 ILMN_1700515ILMN_1700515 C17orf58C17 O58 chromosome17openreadingframe58 chromosome17openreadingframe58 0.02 0.02 -1.62 -1.62 ILMN_2050654ILMN_2050654 SAV1SAV1 salvadorhomolog1(Drosophila) salvadorhomologl (Drosophila) 0.01 0.01 -1.63 -1.63 ILMN_1726288ILMN_1726288 TMEM106BTMEM106B transmembraneprotein106B transmembraneProtein106B 0.00 0.00 -1.63 -1.63 ILMN_3240838ILMN_3240838 SLC25A6SLC25A6 solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6 0.01 0.01 -1.63 -1.63 ILMN_1761275ILMN_1761275 FUT6FUT6 fucosyltransferase 6 (alpha (1,3) fucosyltransferase)fucosyltransferase 6 (alpha (1,3) fucosyltransferase) 0.00 0.00 -1.64 -1.64 ILMN_1687080ILMN_1687080 LOC402251LOC402251 similartoHypotheticalproteinMGC76216 similartoHypotheticalproteinMGC76216 0.04 0.04 -1.64 -1.64 ILMN_1757872ILMN_1757872 DKFZp761P0423DKFZp761P0423 homolog of rat pragma of Rnd2homolog of rat pragma of Rnd2 0.04 0.04 -1.64 -1.64 ILMN_1682812ILMN_1682812 C21orf33C21orf33 chromosome21openreadingframe33 chromosome21openreadingframe33 0.03 0.03 -1.65 -1.65 ILMN_2077905ILMN_2077905 PTGFRNPTGFRN prostaglandinF2receptornegativeregulator prostaglandinF2receptornegativeregulator 0.01 0.01 -1.68 -1.68 ILMN_1715680ILMN_1715680 NEIL2NEIL2 nei endonuclease VIII-like 2 (E. coli)nei endonuclease VIII-like 2 (E. coli) 0.00 0.00 -1.69 -1.69 ILMN_1786823ILMN_1786823 ICAM2ICAM2 intercellular adhesion molecule 2intercellular adhesion molecule 2 0.03 0.03 -1.70 -1.70 ILMN_1811648ILMN_1811648 DCAKDDCAKD dephospho-CoAkinasedomaincontaining dephospho-CoAkinasedomaincontaining 0.01 0.01 -1.71 -1.71 ILMN_3278506ILMN_3278506 LOC148430LOC148430 ribosomalproteinS2pseudogene ribosomalproteinS2pseudogene 0.03 0.03 -1.71 -1.71 ILMN_1660439ILMN_1660439 LOC651149LOC651149 similarto60SribosomalproteinL3(L4) similarto60Sribosomalprotein L3 (L4) 0.05 0.05 -1.72 -1.72 ILMN_1788961ILMN_1788961 PPP2R2APPP2R2A proteinphosphatase2,regulatorysubunitB,alpha proteinphosphatase2, regulatorysubunit B, alpha 0.02 0.02 -1.72 -1.72 ILMN_3235148ILMN_3235148 FLJ43681FLJ43681 ribosomalproteinL23apseudogene ribosomalprotein L23apseudogene 0.01 0.01 -1.74 -1.74 ILMN_1793146ILMN_1793146 CCDC25CCDC25 coiled-coildomaincontaining25 coiled-coildomaincontaining25 0.04 0.04 -1.75 -1.75 ILMN_1656134ILMN_1656134 CNOT7CNOT7 CCR4-NOT transcription complex, subunit 7CCR4-NOT transcription complex, subunit 7 0.02 0.02 -1.75 -1.75 ILMN_1719975ILMN_1719975 HOXC4HOXC4 homeoboxC4 homeoboxC4 0.04 0.04 -1.77 -1.77 ILMN_1677385ILMN_1677385 C8orf40C8orf40 chromosome8openreadingframe40 chromosome8openreadingframe40 0.02 0.02 -1.78 -1.78 ILMN_1764769ILMN_1764769 VWA5AVWA5A vonWillebrandfactorAdomaincontaining5A vonWillebrandfactorAdomaincontaining5A 0.03 0.03 -1.79 -1.79 ILMN_1679483ILMN_1679483 INTS10INTS10 integratorcomplexsubunit10 integratorComplexSubUnit10 0.02 0.02 -1.80 -1.80 ILMN_1653793ILMN_1653793 PDPK1PDPK1 3-phosphoinositidedependentproteinkinase-1 3-phosphoinositideependentproteininase-1 0.03 0.03 -1.82 -1.82 ILMN_1718961ILMN_1718961 BNIP3LBNIP3L BCL2/adenovirusE1B19kDainteractingprotein3-like BCL2 / adenovirusE1B19kDainteractingprotein3-like 0.01 0.01 -1.82 -1.82 ILMN_1759117ILMN_1759117 XKXK X-linked Kx blood group (McLeod syndrome)X-linked Kx blood group (McLeod syndrome) 0.04 0.04 -1.85 -1.85 ILMN_1813641ILMN_1813641 C9orf167C9orf167 chromosome9openreadingframe167 chromosome9openreadingframe167 0.03 0.03 -1.86 -1.86 ILMN_1748908ILMN_1748908 PROSCPROSC proline synthetase co-transcribed homolog (bacterial)proline synthetase co-transcribed homolog (bacterial) 0.01 0.01 -1.89 -1.89 ILMN_1661599ILMN_1661599 DDIT4DDIT4 DNA-damage-inducible transcript 4DNA-damage-inducible transcript 4 0.02 0.02 -1.90 -1.90 ILMN_1725912ILMN_1725912 KLK12KLK12 kallikrein-relatedpeptidase12 kallikrein-relatedpeptidase12 0.04 0.04 -1.94 -1.94 ILMN_3289745ILMN_3289745 LOC339352LOC339352 cytosolic thiouridylase subunit 1 homolog (S. pombe) pseudogenecytosolic thiouridylase subunit 1 homolog (S. pombe) pseudogene 0.00 0.00 -2.07 -2.07 ILMN_2144088ILMN_2144088 FDFT1FDFT1 farnesyl-diphosphatefarnesyltransferase1 farnesyl-diphosphatefarnesyltransferase 1 0.00 0.00 -2.08 -2.08 ILMN_1740234ILMN_1740234 GSTO2GSTO2 glutathione S-transferase omega 2glutathione S-transferase omega 2 0.02 0.02 -2.12 -2.12 ILMN_1802888ILMN_1802888 ZNF185ZNF185 zinc finger protein 185 (LIM domain)zinc finger protein 185 (LIM domain) 0.05 0.05 -2.12 -2.12 ILMN_1741096ILMN_1741096 FDFT1FDFT1 farnesyl-diphosphate farnesyltransferase 1farnesyl-diphosphate farnesyltransferase 1 0.01 0.01 -2.16 -2.16 ILMN_1815032ILMN_1815032 SOX7SOX7 SRY-box containing gene 7SRY-box containing gene 7 0.02 0.02 -2.20 -2.20 ILMN_1757350ILMN_1757350 CTNNB1CTNNB1 catenin(cadherin-associatedprotein),beta1,88kDa catenin (cadherin-associated protein), beta1, 88kDa 0.04 0.04 -2.21 -2.21 ILMN_1746396ILMN_1746396 CTNNB1CTNNB1 catenin(cadherin-associatedprotein),beta1,88kDa catenin (cadherin-associated protein), beta1, 88kDa 0.04 0.04 -2.21 -2.21 ILMN_1684873ILMN_1684873 ARSDARSD arsenical resistance operon trans-acting repressorarsenical resistance operon trans-acting repressor 0.02 0.02 -2.28 -2.28 ILMN_1741755ILMN_1741755 TRIM29TRIM29 tripartitemotifcontaining29 tripartitemotifcontaining29 0.03 0.03 -2.44 -2.44 ILMN_1686920ILMN_1686920 CCDC58CCDC58 coiled-coildomaincontaining58 coiled-coildomaincontaining58 0.03 0.03 -2.84 -2.84 ILMN_1686573ILMN_1686573 DEFB1DEFB1 defensin,beta1 defensin, beta1 0.03 0.03 -3.10 -3.10 ILMN_1720433ILMN_1720433 FAM3DFAM3D family with sequence similarity 3, member Dfamily with sequence similarity 3, member D 0.03 0.03 -3.49 -3.49 ILMN_1689146ILMN_1689146 GABRPGABRP gamma-aminobutyricacid(GABA)Areceptor,pi gamma-aminobutyricacid (GABA) Areceptor, pi 0.05 0.05 -4.07 -4.07 ILMN_1725139ILMN_1725139 CA9CA9 carbonicanhydraseIX carbonicanhydraseIX 0.02 0.02 -4.94 -4.94

실시예Example 2. 유전자들의 기능 확인 2. Identification of genes function

143개의 유전자의 유전자 온톨로지 분석을 통해 기능을 확인하였다(도 2 참조).The function was confirmed by analyzing the gene ontology of 143 genes (see FIG. 2).

cell death, apoptosis, cell adhesion과 cytoskeleton에 관계된 유전자들이 많은 것을 알 수 있다.cell death, apoptosis, cell adhesion, and cytoskeleton.

이것은 Intercellular adhesion의 감소, cell to matrix adhesion의 증가, apoptosis에 대한 저항 등 암의 악성 또는 전이를 나타내는 중요한 특성들로 설명할 수 있다.This can be explained by the important characteristics of cancer malignancy or metastasis, such as decreased intercellular adhesion, increased cell to matrix adhesion, and resistance to apoptosis.

ICAM3, MICB, CD6, NINJ2, SLC27A3, TNC 등의 adhesion에 관계하는 유전자들이 림프절 전이 병기1 (N1)인 환자군에서 증가하였다.The adhesion related genes such as ICAM3, MICB, CD6, NINJ2, SLC27A3 and TNC increased in the patients with lymph node metastasis stage 1 (N1).

cell death와 관계있는 TNFRSF10A, PDCD2, RAC1, DDIT, TMEM173 등의 유전자는 림프절 전이 병기1 (N1)인 환자군에서 감소하였다. 또한 pathway 분석으로 많은 유전자가 세포 생존과 증식에 관계되는 Akt/GSK3β/β-catenin pathway에 관련되어 있는 것을 확인하였다.
The genes related to cell death such as TNFRSF10A, PDCD2, RAC1, DDIT and TMEM173 were decreased in patients with lymph node metastasis stage 1 (N1). In addition, pathway analysis confirmed that many genes are involved in the Akt / GSK3β / β-catenin pathway involved in cell survival and proliferation.

Claims

시알리다아제 1(sialidase 1, NEU1) 유전자의 발현 수준을 측정하는 제제를 포함하는, 위암의 림프절 전이 진단용 조성물.
A composition for diagnosing lymph node metastasis in gastric cancer, comprising an agent for measuring the expression level of a sialidase 1 (NEU1) gene.

청구항 1에 있어서, 상기 제제는 HLA-DRB5(major histocompatibility complex, class II, DR beta 5), DACH1(dachshund homolog 1), IRX3(iroquois homeobox 3), CD7(CD7 antigen), YBX2(Ybox binding protein 2), HOXA11AS(HOXA11 antisense RNA), ITPKA(inositol-trisphosphate 3-kinase A), MICB(MHC class I polypeptide-related sequence B), ENO3(enolase3,betamuscle), ARID3A(AT rich interactive domain 3A), LTB(lymphotoxinbeta), NINJ2(ninjurin2), C20orf100(TOX high mobility group box family member 2), NES(nestin), CENPN(centromere protein N), ARHGAP4(RhoGTPase activating protein 4), FAM69B(family with sequence similarity 69, member B), SLC27A3(solute carrier family 27 (fatty acid transporter), member 3), EFCAB4A(EF-hand calcium binding domain 4A), KIFC1(kinesin family member C1), RASAL3(RAS protein activator like 3), ABCB1(ATP-binding cassette, sub-family B (MDR/TAP), member 1), FOXA3(forkheadboxA3), TEAD4(TEA domain family member 4), CKS1B(CDC28 protein kinase regulatory subunit 1B), SLC39A8(solute carrier family 39 (metal ion transporter), member 8), TNC(tenascin C), ELOVL5(ELOVL fatty acid elongase 5), LOC730102(quinone oxidoreductase-like protein 2 pseudogene), SLC26A6(solute carrier family 26, member 6), AURKA(aurora kinase A), ICAM3(intercellular adhesion molecule 3), LOC729086(vesicular, overexpressed in cancer, prosurvival protein 1 pseudogene), FYN(FYN oncogene related to SRC,FGR,YES), FLJ35776(uncharacterized LOC649446), SHD(src homology 2 domain-containing transforming protein D), BRI3BP(BRI3 binding protein) , SLC37A4(solute carrier family 37 (glucose-6-phosphate transporter), member 4), INPP5E(inositol polyphosphate-5-phosphatase), HIST1H4H(histone cluster1,H4h), GTF3A(general transcription factor IIIA), C13orf23(proline and serine rich1), MLH1(mutLhomolog1,coloncancer,nonpolyposistype2(E.coli)), CD96(CD96 antigen), GRTP1(GH regulated TBC protein 1), ETS1(v-ets erythroblastosis virus E26 oncogenehomolog1 (avian)), FOXM1(forkheadboxM1), TMEM156(transmembrane protein 156), EXOSC8(exosome component 8), ZC3H3(CG6694 gene product from transcript CG6694-RA), LOC646753(ribosomal protein S26 pseudogene 2), ESPN(espin), FLOT1(flotillin1), DTNA(dystrobrevin,alpha), SPTBN5(spectrin, beta, non-erythrocytic 5), KBTBD12(kelch repeat and BTB (POZ) domain containing 12), VARS2(valyl-tRNA synthetase 2, mitochondrial (putative)), CD6(CD6 antigen), CENPJ(centromere protein J), PIGP(phosphatidylinositol glycan anchor biosynthesis, class P), LOC440595(eukaryotic translation elongation factor 1 alpha 1 pseudogene 11)), LOC653650(3-phosphoinositide dependent protein kinase 1 pseudogene), BSPRY(B-box and SPRY domain containing), ALDH6A1(aldehyde dehydrogenase 6 family, member A1), MRPL43(mitochondrial ribosomal protein L43), C11orf74(chromosome 11 open reading frame 74), PDCD2(programmed cell death 2), RAC1(ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), PCM1(pericentriolarmaterial1), HEPACAM2(HEPACAM family member2), IFT20(intraflagellar transport 20 homolog (Chlamydomonas)), TMEM173(transmembrane protein 173), SH2D4A(SH2 domain containing 4A), ERLIN2(ER lipid raft associated 2), NXF3(nuclear RNA export factor 3), ABTB1(ankyrin repeat and BTB (POZ) domain containing 1), MCPH1(microcephalin 1), TNFRSF10B(tumor necrosis factor receptor superfamily, member10b), PCBD1(pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha), SDC1(syndecan 1), EXTL3(exostoses (multiple)-like 3), SLC38A10(solute carrier family 38, member 10), ZNF395(zinc finger protein395), C17orf58(chromosome 17 open reading frame 58), PTGFRN(prostaglandin F2 receptor negative regulator), WRB(tryptophan rich basic protein), EBP(emopamil binding protein (sterol isomerase)), C14orf4(interferon regulatory factor 2 binding protein-like), TNFRSF10A(tumor necrosis factor receptor superfamily, member 10a) CCDC25(coiled-coil domain containing 25), MIPOL1(mirror-image polydactyly 1), AIG1(androgen-induced1), KCNK1(potassium channel,subfamilyK, member1)), UBXN8(UBX domain protein 8), NRIP1(nuclear receptor interacting protein 1), TFG(TRK-fusedgene), APPBP2(amyloid beta precursor protein (cytoplasmic tail) binding protein 2), IFT74(intraflagellar transport 74 homolog(Chlamydomonas), DSG2(desmoglein 2), ASMTL(acetyl serotonin O-methyl transferase-like), TMEM66(transmembrane protein 66), C21orf33(chromosome 21 open reading frame33), WDR23(WD40repeat-containing protein), TKT(transketolase), SAV1(salvador homolog 1(Drosophila)), TMEM106B(transmembrane protein 106B), SLC25A6(solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6), FUT6(fucosyltransferase 6 (alpha (1,3) fucosyltransferase)), LOC402251(similar to Hypothetical protein MGC76216), DKFZp761P0423(homolog of rat pragma of Rnd2), NEIL2(nei endonuclease VIII-like 2 (E. coli)), ICAM2(intercellular adhesion molecule 2), DCAKD(dephospho-CoA kinase domain containing), LOC148430(ribosomal protein S2 pseudogene), LOC651149(similar to 60S ribosomal protein L3(L4)), PPP2R2A(protein phosphatase 2,regulatory subunit B,alpha), FLJ43681(ribosomal protein L23a pseudogene), CNOT7(CCR4-NOT transcription complex, subunit 7), HOXC4(homeoboxC4), C8orf40(chromosome 8 open reading frame40), VWA5A(von Willebrand factor A domain containing 5A), INTS10(integrator complex subunit 10), PDPK1(3-phosphoinositide dependent protein kinase-1), BNIP3L(BCL2/adenovirus E1B 19kDa interacting protein 3-like), XK(X-linked Kx blood group (McLeod syndrome)), C9orf167(chromosome 9 open reading frame 167), PROSC(proline synthetase co-transcribed homolog (bacterial)), DDIT4(DNA-damage-inducible transcript 4), KLK12(kallikrein-related peptidase 12), LOC339352(cytosolic thiouridylase subunit 1 homolog (S. pombe) pseudogene), FDFT1(farnesyl-diphosphate farnesyl transferase1), GSTO2(glutathione S-transferase omega 2), ZNF185(zinc finger protein 185 (LIM domain)), SOX7(SRY-box containing gene 7), CTNNB1(catenin(cadherin-associated protein),beta1,88kDa), ARSD(arsenical resistance operon trans-acting repressor), TRIM29(tripartite motif containing 29), CCDC58(coiled-coil domain containing 58), DEFB1(defensin,beta1), FAM3D(family with sequence similarity 3, member D), GABRP(gamma-aminobutyric acid(GABA) A receptor,pi) 및 CA9(carbonic anhydrase IX)로 이루어진 군에서 선택되는 하나 이상의 유전자의 발현 수준을 측정하는 제제를 더 포함하는, 위암의 림프절 전이 진단용 조성물.
The composition according to claim 1, wherein the preparation is selected from the group consisting of HLA-DRB5 (major histocompatibility complex, class II, DR beta 5), dachshund homolog 1, IRX3, CD7 antigen, YBX2 ), HOXA11AS (HOXA11 antisense RNA), ITPKA (inositol-trisphosphate 3-kinase A), MICB (MHC class I polypeptide-related sequence B), ENO3 (enolase3, betamuscle), ARID3A lymphotoxinbeta), NINJ2 (ninjurin2), C20orf100 (TOX high mobility group box member 2), NES (nestin), CENPN (centromere protein N), ARHGAP4 (RhoGTPase activating protein 4), FAM69B ), SLC27A3 (solute carrier family 27, fatty acid transporter 3), EFABAB4A (EF-hand calcium binding domain 4A), KIFC1 (kinesin family member C1), RAS protein activator like 3, ABCB1 binding cassette, sub-family B (MDR / TAP), member 1), FOXA3 (forkheadboxA3), TEAD4 (TEA domain family member 4), CKS1B (CDC28 protein kinase regulatory subunit 1B), SLC39A8 lute carrier family 39 (metal ion transporter), member 8), TNC (tenascin C), ELOVL5 (ELOVL fatty acid elongase 5), LOC730102 (quinone oxidoreductase-like protein 2 pseudogene), SLC26A6 (solute carrier family 26, member 6) , AURKA (aurora kinase A), ICAM3 (intercellular adhesion molecule 3), LOC729086 (vesicular, overexpressed in cancer, prosurvival protein 1 pseudogene), FYN (FYN oncogene related to SRC, FGR, YES), FLJ35776 (uncharacterized LOC649446) (BRI3BP), SLC37A4 (solute carrier family 37 (glucose-6-phosphate transporter), member 4), INPP5E (inositol polyphosphate-5-phosphatase), HIST1H4H (CD96 antigen), GRTP1 (GH regulated Tb protein 1), and GH regulated T cell protein 1 (GH regulatory T cell protein 1) , ETS1 (v-ets erythroblastosis virus E26 oncogenehomolog1 (avian)), FOXM1 (forkheadboxM1), TMEM156 (transmembrane prote LOC646753 (ribosomal protein S26 pseudogene 2), ESPN (espin), FLOT1 (flotillin1), DTNA (dystrobrevin, alpha), SPTBN5 (exotoxin 8), EXOSC8 (exosome component 8), ZC3H3 (CG6694 gene product from transcript CG6694- VARS2 (valyl-tRNA synthetase 2, mitochondrial (putative)), CD6 (CD6 antigen), CENPJ (centromere protein J ), PIGP (phosphatidylinositol glycan anchor biosynthesis, class P), LOC440595 (eukaryotic translation elongation factor 1 alpha 1 pseudogene 11), LOC653650 (3-phosphoinositide dependent protein kinase 1 pseudogene), BSPRY Related mitochondrial toxin substrate 1 (rho family), RL1 (rho-related C3), ALDH6A1 (aldehyde dehydrogenase 6 family member A1), MRPL43 (mitochondrial ribosomal protein L43), C11orf74 (chromosome 11 open reading frame 74) , small GTP binding protein Rac1), PCM1 (pericentriolarmaterial1), HEPACAM2 (HEPACAM family member2), IFT20 (in (NF), ABFB1 (ankyrin repeat and BTB (POZ)), EGFR2 (EGFR2), EGFR2 ) domain containing 1), MCPH1 (microcephalin 1), TNFRSF10B (tumor necrosis factor receptor superfamily, member10b), PCBD1 (pterin-4 alpha-carbinolamine dehydratase / dimerization cofactor of hepatocyte nuclear factor 1 alpha), SDC1 (exostoses (multiple) -like 3), SLC38A10 (solute carrier family 38, member 10), ZNF395 (zinc finger protein 395), C17orf58 (chromosome 17 open reading frame 58), PTGFRN (prostaglandin F2 receptor negative regulator), WRB rich basic protein, EBP (emopamil binding protein (sterol isomerase)), C14orf4 (interferon regulatory factor 2 binding protein-like), tumor necrosis factor receptor superfamily (member 10a) CCDC25 (coiled- (mirror-image polydactyly 1), AIG1 (androgen-induced 1), K UBX domain protein 8, nuclear receptor interacting protein 1 (NRIP1), TRK-fusedgene (TFG), APPBP2 (amyloid beta precursor protein (cytoplasmic tail) binding protein 2) (Open reading frame 33), WDR40 (WD40repeat-containing protein), IFT74 (intraflagellar transport 74 homolog (Chlamydomonas), DSG2 (desmoglein 2), ASMTL (acetyl serotonin O- methyl transferase- ), TKT (transketolase), SAV1 (salvador homolog 1 (Drosophila)), TMEM106B (transmembrane protein 106B), SLC25A6 (solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator, member 6), FUT6 (fucosyltransferase 6 (alpha (1,3) fucosyltransferase), LOC402251 (similar to Hypothetical protein MGC76216), DKFZp761P0423 (homolog of rat pragma of Rnd2), NEIL2 (nei endonuclease VIII- (Ribosomal protein S2 pseudogene), LOC651149 (similar to 60S ribosomal protein L3 (L4)), PPP2R2A (protein of the present invention), ICAM2 (intercellular adhesion molecule 2), DCAKD (dephospho-CoA kinase domain containing) phosphatase 2, regulatory subunit B, alpha), FLJ43681 (ribosomal protein L23a pseudogene), CNOT7 (CCR4-NOT transcription complex, subunit 7), HOXC4 (homeoboxC4), C8orf40 (chromosome 8 open reading frame40), VWA5A domain containing 5A), integrator complex subunit 10 (INTS10), 3-phosphoinositide dependent protein kinase-1 (PDPK1), BNIP3L (BCL2 / adenovirus E1B 19kDa interacting protein 3-like), XK (X-linked Kx blood group ), C9orf167 (chromosome 9 open reading frame 167), PROSC (proline synthetase co-transcribed homo (DNA-damage-inducible transcript 4), KLK12 (kallikrein-related peptidase 12), LOC339352 (cytosolic thiouridylase subunit 1 homolog (S. (glutathione S-transferase omega 2), ZNF185 (zinc finger protein 185 (LIM domain)), SOX7 (SRY-box containing gene 7), CTNNB1 (catenin cadherin-associated protein, beta1,88kDa), ARSD (arsenical resistance operon trans-acting repressor), TRIM29 (tripartite motif containing 29), CCDC58 (coiled-coil domain containing 58), DEFB1 (defensin, beta1), FAM3D (GABA) A receptor, pi) and CA9 (carbonic anhydrase IX), wherein the expression level of at least one gene selected from the group consisting of GABA (GABA) with sequence similarity 3, member D), GABRP (gamma-aminobutyric acid , A composition for diagnosing lymph node metastasis of gastric cancer.

청구항 1에 있어서, 위암의 림프절 전이 병기에 대한 진단이 가능한, 위암의 림프절 전이 진단용 조성물.
The composition for diagnosing lymph node metastasis of gastric cancer according to claim 1, which is capable of diagnosing a lymph node metastasis stage of gastric cancer.

청구항 1 내지 3 중 어느 한 항에 있어서, 상기 제제는 상기 하나 이상의 유전자에 특이적으로 결합하는 프라이머, 프로브 또는 앱타머를 포함하는 것인, 조성물.
The composition according to any one of claims 1 to 3, wherein the agent comprises a primer, a probe or an aptamer that specifically binds to the one or more genes.

청구항 1 내지 3 중 어느 한 항의 조성물을 포함하는 위암의 림프절 전이 진단용 키트.
A kit for the diagnosis of lymph node metastasis of gastric cancer comprising the composition of any one of claims 1 to 3.

청구항 5에 있어서, 마이크로어레이, RT-PCR 또는 면역분석방식에 의한 것인, 키트.
6. The kit according to claim 5, which is by microarray, RT-PCR or immunoassay.

위암의 림프절 전이가 의심되는 환자의 시료의 시알리다아제 1(sialidase 1, NEU1) 유전자의 발현 수준을 측정하는 단계; 및
상기 유전자의 발현 수준을 정상 대조구 시료의 해당 유전자의 발현 수준과 비교하는 단계
를 포함하는, 위암의 림프절 전이 진단을 위한 정보 제공 방법.
Measuring the expression level of sialidase 1 (NEU1) gene of a sample of a patient suspected of having lymph node metastasis of gastric cancer; And
Comparing the expression level of the gene with the expression level of the corresponding gene of the normal control sample
Of the gastric cancer.

청구항 7에 있어서, HLA-DRB5(major histocompatibility complex, class II, DR beta 5), DACH1(dachshund homolog 1), IRX3(iroquois homeobox 3), CD7(CD7 antigen), YBX2(Ybox binding protein 2), HOXA11AS(HOXA11 antisense RNA), ITPKA(inositol-trisphosphate 3-kinase A), MICB(MHC class I polypeptide-related sequence B), ENO3(enolase3,betamuscle), ARID3A(AT rich interactive domain 3A), LTB(lymphotoxinbeta), NINJ2(ninjurin2), C20orf100(TOX high mobility group box family member 2), NES(nestin), CENPN(centromere protein N), ARHGAP4(RhoGTPase activating protein 4), FAM69B(family with sequence similarity 69, member B), SLC27A3(solute carrier family 27 (fatty acid transporter), member 3), EFCAB4A(EF-hand calcium binding domain 4A), KIFC1(kinesin family member C1), RASAL3(RAS protein activator like 3), ABCB1(ATP-binding cassette, sub-family B (MDR/TAP), member 1), FOXA3(forkheadboxA3), TEAD4(TEA domain family member 4), CKS1B(CDC28 protein kinase regulatory subunit 1B), SLC39A8(solute carrier family 39 (metal ion transporter), member 8), TNC(tenascin C), ELOVL5(ELOVL fatty acid elongase 5), LOC730102(quinone oxidoreductase-like protein 2 pseudogene), SLC26A6(solute carrier family 26, member 6), AURKA(aurora kinase A), ICAM3(intercellular adhesion molecule 3), LOC729086(vesicular, overexpressed in cancer, prosurvival protein 1 pseudogene), FYN(FYN oncogene related to SRC,FGR,YES), FLJ35776(uncharacterized LOC649446), SHD(src homology 2 domain-containing transforming protein D), BRI3BP(BRI3 binding protein) , SLC37A4(solute carrier family 37 (glucose-6-phosphate transporter), member 4), INPP5E(inositol polyphosphate-5-phosphatase), HIST1H4H(histone cluster1,H4h), GTF3A(general transcription factor IIIA), C13orf23(proline and serine rich1), MLH1(mutLhomolog1,coloncancer,nonpolyposistype2(E.coli)), CD96(CD96 antigen), GRTP1(GH regulated TBC protein 1), ETS1(v-ets erythroblastosis virus E26 oncogenehomolog1 (avian)), FOXM1(forkheadboxM1), TMEM156(transmembrane protein 156), EXOSC8(exosome component 8), ZC3H3(CG6694 gene product from transcript CG6694-RA), LOC646753(ribosomal protein S26 pseudogene 2), ESPN(espin), FLOT1(flotillin1), DTNA(dystrobrevin,alpha), SPTBN5(spectrin, beta, non-erythrocytic 5), KBTBD12(kelch repeat and BTB (POZ) domain containing 12), VARS2(valyl-tRNA synthetase 2, mitochondrial (putative)), CD6(CD6 antigen), CENPJ(centromere protein J), PIGP(phosphatidylinositol glycan anchor biosynthesis, class P), LOC440595(eukaryotic translation elongation factor 1 alpha 1 pseudogene 11)), LOC653650(3-phosphoinositide dependent protein kinase 1 pseudogene), BSPRY(B-box and SPRY domain containing), ALDH6A1(aldehyde dehydrogenase 6 family, member A1), MRPL43(mitochondrial ribosomal protein L43), C11orf74(chromosome 11 open reading frame 74), PDCD2(programmed cell death 2), RAC1(ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), PCM1(pericentriolarmaterial1), HEPACAM2(HEPACAM family member2), IFT20(intraflagellar transport 20 homolog (Chlamydomonas)), TMEM173(transmembrane protein 173), SH2D4A(SH2 domain containing 4A), ERLIN2(ER lipid raft associated 2), NXF3(nuclear RNA export factor 3), ABTB1(ankyrin repeat and BTB (POZ) domain containing 1), MCPH1(microcephalin 1), TNFRSF10B(tumor necrosis factor receptor superfamily, member10b), PCBD1(pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha), SDC1(syndecan 1), EXTL3(exostoses (multiple)-like 3), SLC38A10(solute carrier family 38, member 10), ZNF395(zinc finger protein395), C17orf58(chromosome 17 open reading frame 58), PTGFRN(prostaglandin F2 receptor negative regulator), WRB(tryptophan rich basic protein), EBP(emopamil binding protein (sterol isomerase)), C14orf4(interferon regulatory factor 2 binding protein-like), TNFRSF10A(tumor necrosis factor receptor superfamily, member 10a) CCDC25(coiled-coil domain containing 25), MIPOL1(mirror-image polydactyly 1), AIG1(androgen-induced1), KCNK1(potassium channel,subfamilyK, member1)), UBXN8(UBX domain protein 8), NRIP1(nuclear receptor interacting protein 1), TFG(TRK-fusedgene), APPBP2(amyloid beta precursor protein (cytoplasmic tail) binding protein 2), IFT74(intraflagellar transport 74 homolog(Chlamydomonas), DSG2(desmoglein 2), ASMTL(acetyl serotonin O-methyl transferase-like), TMEM66(transmembrane protein 66), C21orf33(chromosome 21 open reading frame33), WDR23(WD40repeat-containing protein), TKT(transketolase), SAV1(salvador homolog 1(Drosophila)), TMEM106B(transmembrane protein 106B), SLC25A6(solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6), FUT6(fucosyltransferase 6 (alpha (1,3) fucosyltransferase)), LOC402251(similar to Hypothetical protein MGC76216), DKFZp761P0423(homolog of rat pragma of Rnd2), NEIL2(nei endonuclease VIII-like 2 (E. coli)), ICAM2(intercellular adhesion molecule 2), DCAKD(dephospho-CoA kinase domain containing), LOC148430(ribosomal protein S2 pseudogene), LOC651149(similar to 60S ribosomal protein L3(L4)), PPP2R2A(protein phosphatase 2,regulatory subunit B,alpha), FLJ43681(ribosomal protein L23a pseudogene), CNOT7(CCR4-NOT transcription complex, subunit 7), HOXC4(homeoboxC4), C8orf40(chromosome 8 open reading frame40), VWA5A(von Willebrand factor A domain containing 5A), INTS10(integrator complex subunit 10), PDPK1(3-phosphoinositide dependent protein kinase-1), BNIP3L(BCL2/adenovirus E1B 19kDa interacting protein 3-like), XK(X-linked Kx blood group (McLeod syndrome)), C9orf167(chromosome 9 open reading frame 167), PROSC(proline synthetase co-transcribed homolog (bacterial)), DDIT4(DNA-damage-inducible transcript 4), KLK12(kallikrein-related peptidase 12), LOC339352(cytosolic thiouridylase subunit 1 homolog (S. pombe) pseudogene), FDFT1(farnesyl-diphosphate farnesyl transferase1), GSTO2(glutathione S-transferase omega 2), ZNF185(zinc finger protein 185 (LIM domain)), SOX7(SRY-box containing gene 7), CTNNB1(catenin(cadherin-associated protein),beta1,88kDa), ARSD(arsenical resistance operon trans-acting repressor), TRIM29(tripartite motif containing 29), CCDC58(coiled-coil domain containing 58), DEFB1(defensin,beta1), FAM3D(family with sequence similarity 3, member D), GABRP(gamma-aminobutyric acid(GABA) A receptor,pi) 및 CA9(carbonic anhydrase IX)로 이루어진 군에서 선택되는 하나 이상의 유전자의 발현 수준을 측정하는 단계; 및
상기 하나 이상의 유전자의 발현 수준을 정상 대조구 시료의 해당 유전자의 발현 수준과 비교하는 단계를 더 포함하는, 방법.
The method according to claim 7, wherein HLA-DRB5 (major histocompatibility complex, class II, DR beta 5), DACH1 (dachshund homolog 1), IRX3 (iroquois homeobox 3), CD7 (CD7 antigen), YBX2 (HOXA11 antisense RNA), inositol-trisphosphate 3-kinase A (ITPKA), MHC class I polypeptide-related sequence B, ENO3 (enolase3, betamuscle), ARID3A (AT rich interactive domain 3A), LTB (lymphotoxinbeta) NINJ2 (ninjurin2), C20orf100 (TOX high mobility group box family member 2), NES (nestin), CENPN (centromere protein N), ARHGAP4 (RhoGTPase activating protein 4), FAM69B (family with sequence similarity 69, member B) (AFT-binding cassette), ABCB1 (ATP-binding cassette), KIFC1 (kinesin family member C1), RASAL3 (RAS protein activator like 3) (CDR2 protein kinase regulatory subunit 1B), SLC39A8 (solute carrier fami 1), subtype B (MDR / TAP), member 1), FOXA3 (forkheadboxA3), TEAD4 ly 39 (metal ion transporter), member 8), TNC (tenascin C), ELOVL5 (ELOVL fatty acid elongase 5), LOC730102 (quinone oxidoreductase-like protein 2 pseudogene), SLC26A6 (solute carrier family 26, member 6) aurora kinase A, intercellular adhesion molecule 3 (ICAM3), LOC729086 (vesicular overexpressed cancer, prosurvival protein 1 pseudogene), FYN (FYN oncogene related to SRC, FGR, YES), FLJ35776 (uncharacterized LOC649446) homology 2 domain-containing transforming protein D), BRI3BP (BRI3 binding protein), SLC37A4 (solute carrier family 37, member 4), INPP5E (inositol polyphosphate-5-phosphatase), HIST1H4H , H4h), GTF3A (general transcription factor IIIA), C13orf23 (proline and serine rich1), MLH1 (mutLhomolog1, coloncancer, nonpolyposistype2 (E. coli)), CD96 (CD96 antigen), GRTP1 (GH regulated TBC protein 1) (v-ets erythroblastosis virus E26 oncogenehomolog1 (avian)), FOXM1 (forkheadboxM1), TMEM156 (transmembrane protein 156), EXOSC8 SPOTBN5 (spectrin, beta, non)), LOC646753 (ribosomal protein S26 pseudogene 2), ESPN (espin), FLOT1 (flotillin1), DTNA (dystrobrevin, alpha), ZC3H3 (CG6694 gene product from transcript CG6694- (cysteine-5), KBTBD12 (kelch repeat and BTB (POZ) domain containing 12), VARS2 (valyl-tRNA synthetase 2, mitochondrial (putative)), CD6 (CD6 antigen), CENPJ (centromere protein J), phosphatidylinositol glycan anchor biosynthesis class P), LOC440595 (eukaryotic translation elongation factor 1 alpha 1 pseudogene 11)), LOC653650 (3-phosphoinositide dependent protein kinase 1 pseudogene), BSPRY (B-box and SPRY domain containing), ALDH6A1 (aldehyde dehydrogenase 6 family , member A1), MRPL43 (mitochondrial ribosomal protein L43), C11orf74 (chromosome 11 open reading frame 74), PDCD2 (programmed cell death 2), RAC1 (ras-related C3 botulinum toxin substrate 1 ), PCM1 (pericentriolarmaterial1), HEPACAM2 (HEPACAM family member2), IFT20 (intraflagellar tran (20), NKF3 (nuclear RNA export factor 3), ABTB1 (ankyrin repeat and BTB (POZ)), EGFR2 (PTCA1), SDC1 (syndecan 1), EXTL3 (paclitaxel), and paclitaxel (paclitaxel) exostoses (multiple) -like 3), SLC38A10 (solute carrier family 38, member 10), ZNF395 (zinc finger protein 395), C17orf58 (chromosome 17 open reading frame 58), PTGFRN (prostaglandin F2 receptor negative regulator), WRB basic protein), EBP (emopamil binding protein (sterol isomerase)), C14orf4 (interferon regulatory factor 2 binding protein-like), TNFRSF10A (tumor necrosis factor receptor superfamily, member 10a) CCDC25 mirror-image polydactyly 1), AIG1 (androgen-induced 1), KCNK1 (potassium ch annel, subfamilyK, member1), UBX domain protein 8, NRIP1, TRK-fusedgene, APPBP2 (cytoplasmic tail binding protein 2), IFT74 (intraflagellar transport 74 homolog (Chlamydomonas), DSG2 (desmoglein 2), ASMTL (acetyl serotonin O-methyl transferase-like), TMEM66 (transmembrane protein 66), C21orf33 (chromosome 21 open reading frame33), WDR23 (WD40repeat- (transketolase), SAV1 (salvador homolog 1 (Drosophila)), TMEM106B (transmembrane protein 106B), SLC25A6 (solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator, member 6), FUT6 (fucosyltransferase 6 (alpha (1,3) fucosyltransferase), LOC402251 (similar to Hypothetical protein MGC76216), DKFZp761P0423 (homolog of rat pragma of Rnd2), NEIL2 (nei endonuclease VIII- (Ribosomal protein S2 pseudogene), LOC651149 (similar to 60S ribosomal protein L3 (L4)), PPP2R2A (protein of the present invention), ICAM2 (intercellular adhesion molecule 2), DCAKD (dephospho-CoA kinase domain containing) phosphatase 2, regulatory subunit B, alpha), FLJ43681 (ribosomal protein L23a pseudogene), CNOT7 (CCR4-NOT transcription complex, subunit 7), HOXC4 (homeoboxC4), C8orf40 (chromosome 8 open reading frame40), VWA5A domain containing 5A), integrator complex subunit 10 (INTS10), 3-phosphoinositide dependent protein kinase-1 (PDPK1), BNIP3L (BCL2 / adenovirus E1B 19kDa interacting protein 3-like), XK (X-linked Kx blood group ), C9orf167 (chromosome 9 open reading frame 167), PROSC (proline synthetase co-transcribed homo (DNA-damage-inducible transcript 4), KLK12 (kallikrein-related peptidase 12), LOC339352 (cytosolic thiouridylase subunit 1 homolog (S. (glutathione S-transferase omega 2), ZNF185 (zinc finger protein 185 (LIM domain)), SOX7 (SRY-box containing gene 7), CTNNB1 (catenin cadherin-associated protein, beta1,88kDa), ARSD (arsenical resistance operon trans-acting repressor), TRIM29 (tripartite motif containing 29), CCDC58 (coiled-coil domain containing 58), DEFB1 (defensin, beta1), FAM3D measuring the expression level of one or more genes selected from the group consisting of with sequence similarity 3, member D, GABRP (gamma-aminobutyric acid (GABA) A receptor, pi) and CA9 (carbonic anhydrase IX) And
And comparing the expression level of said one or more genes with an expression level of a corresponding gene of a normal control sample.

청구항 7에 있어서, 상기 정보는 위암의 림프절 전이 병기에 대한 것인, 정보 제공 방법.
8. The method of claim 7, wherein the information is for a lymph node metastasis stage of gastric cancer.

청구항 7 내지 9 중 어느 한 항에 있어서, 상기 하나 이상의 유전자의 발현 수준을 측정하는 단계는 마이크로어레이, 역전사효소 중합효소반응, 면역분석방식, 경쟁적 역전사효소 중합효소반응, 실시간 역전사효소 중합효소반응, RNase 보호 분석법 또는 노던 블랏팅에 의한 것인 방법.
The method according to any one of claims 7 to 9, wherein the step of measuring the expression level of the at least one gene comprises the steps of: a microarray, a reverse transcriptase polymerase reaction, an immunoassay, a competitive reverse transcriptase polymerase, RNase protection assay or Northern blotting.

시알리다아제 1(sialidase 1, NEU1) 유전자의 뉴클레오타이드 서열을 포함하는 세포에 분석하고자 하는 시료를 접촉시키는 단계; 및
상기 뉴클레오티드 서열의 발현량을 측정하는 단계를 포함하는 위암의 림프절 전이의 억제 또는 예방용 물질의 스크리닝 방법.
Contacting a sample to be analyzed with a cell containing a nucleotide sequence of a sialidase 1 (NEU1) gene; And
And measuring the expression level of the nucleotide sequence.

청구항 11에 있어서, HLA-DRB5(major histocompatibility complex, class II, DR beta 5), DACH1(dachshund homolog 1), IRX3(iroquois homeobox 3), CD7(CD7 antigen), YBX2(Ybox binding protein 2), HOXA11AS(HOXA11 antisense RNA), ITPKA(inositol-trisphosphate 3-kinase A), MICB(MHC class I polypeptide-related sequence B), ENO3(enolase3,betamuscle), ARID3A(AT rich interactive domain 3A), LTB(lymphotoxinbeta), NINJ2(ninjurin2), C20orf100(TOX high mobility group box family member 2), NES(nestin), CENPN(centromere protein N), ARHGAP4(RhoGTPase activating protein 4), FAM69B(family with sequence similarity 69, member B), SLC27A3(solute carrier family 27 (fatty acid transporter), member 3), EFCAB4A(EF-hand calcium binding domain 4A), KIFC1(kinesin family member C1), RASAL3(RAS protein activator like 3), ABCB1(ATP-binding cassette, sub-family B (MDR/TAP), member 1), FOXA3(forkheadboxA3), TEAD4(TEA domain family member 4), CKS1B(CDC28 protein kinase regulatory subunit 1B), SLC39A8(solute carrier family 39 (metal ion transporter), member 8), TNC(tenascin C), ELOVL5(ELOVL fatty acid elongase 5), LOC730102(quinone oxidoreductase-like protein 2 pseudogene), SLC26A6(solute carrier family 26, member 6), AURKA(aurora kinase A), ICAM3(intercellular adhesion molecule 3), LOC729086(vesicular, overexpressed in cancer, prosurvival protein 1 pseudogene), FYN(FYN oncogene related to SRC,FGR,YES), FLJ35776(uncharacterized LOC649446), SHD(src homology 2 domain-containing transforming protein D), BRI3BP(BRI3 binding protein) , SLC37A4(solute carrier family 37 (glucose-6-phosphate transporter), member 4), INPP5E(inositol polyphosphate-5-phosphatase), HIST1H4H(histone cluster1,H4h), GTF3A(general transcription factor IIIA), C13orf23(proline and serine rich1), MLH1(mutLhomolog1,coloncancer,nonpolyposistype2(E.coli)), CD96(CD96 antigen), GRTP1(GH regulated TBC protein 1), ETS1(v-ets erythroblastosis virus E26 oncogenehomolog1 (avian)), FOXM1(forkheadboxM1), TMEM156(transmembrane protein 156), EXOSC8(exosome component 8), ZC3H3(CG6694 gene product from transcript CG6694-RA), LOC646753(ribosomal protein S26 pseudogene 2), ESPN(espin), FLOT1(flotillin1), DTNA(dystrobrevin,alpha), SPTBN5(spectrin, beta, non-erythrocytic 5), KBTBD12(kelch repeat and BTB (POZ) domain containing 12), VARS2(valyl-tRNA synthetase 2, mitochondrial (putative)), CD6(CD6 antigen), CENPJ(centromere protein J), PIGP(phosphatidylinositol glycan anchor biosynthesis, class P), LOC440595(eukaryotic translation elongation factor 1 alpha 1 pseudogene 11)), LOC653650(3-phosphoinositide dependent protein kinase 1 pseudogene), BSPRY(B-box and SPRY domain containing), ALDH6A1(aldehyde dehydrogenase 6 family, member A1), MRPL43(mitochondrial ribosomal protein L43), C11orf74(chromosome 11 open reading frame 74), PDCD2(programmed cell death 2), RAC1(ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), PCM1(pericentriolarmaterial1), HEPACAM2(HEPACAM family member2), IFT20(intraflagellar transport 20 homolog (Chlamydomonas)), TMEM173(transmembrane protein 173), SH2D4A(SH2 domain containing 4A), ERLIN2(ER lipid raft associated 2), NXF3(nuclear RNA export factor 3), ABTB1(ankyrin repeat and BTB (POZ) domain containing 1), MCPH1(microcephalin 1), TNFRSF10B(tumor necrosis factor receptor superfamily, member10b), PCBD1(pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha), SDC1(syndecan 1), EXTL3(exostoses (multiple)-like 3), SLC38A10(solute carrier family 38, member 10), ZNF395(zinc finger protein395), C17orf58(chromosome 17 open reading frame 58), PTGFRN(prostaglandin F2 receptor negative regulator), WRB(tryptophan rich basic protein), EBP(emopamil binding protein (sterol isomerase)), C14orf4(interferon regulatory factor 2 binding protein-like), TNFRSF10A(tumor necrosis factor receptor superfamily, member 10a) CCDC25(coiled-coil domain containing 25), MIPOL1(mirror-image polydactyly 1), AIG1(androgen-induced1), KCNK1(potassium channel,subfamilyK, member1)), UBXN8(UBX domain protein 8), NRIP1(nuclear receptor interacting protein 1), TFG(TRK-fusedgene), APPBP2(amyloid beta precursor protein (cytoplasmic tail) binding protein 2), IFT74(intraflagellar transport 74 homolog(Chlamydomonas), DSG2(desmoglein 2), ASMTL(acetyl serotonin O-methyl transferase-like), TMEM66(transmembrane protein 66), C21orf33(chromosome 21 open reading frame33), WDR23(WD40repeat-containing protein), TKT(transketolase), SAV1(salvador homolog 1(Drosophila)), TMEM106B(transmembrane protein 106B), SLC25A6(solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6), FUT6(fucosyltransferase 6 (alpha (1,3) fucosyltransferase)), LOC402251(similar to Hypothetical protein MGC76216), DKFZp761P0423(homolog of rat pragma of Rnd2), NEIL2(nei endonuclease VIII-like 2 (E. coli)), ICAM2(intercellular adhesion molecule 2), DCAKD(dephospho-CoA kinase domain containing), LOC148430(ribosomal protein S2 pseudogene), LOC651149(similar to 60S ribosomal protein L3(L4)), PPP2R2A(protein phosphatase 2,regulatory subunit B,alpha), FLJ43681(ribosomal protein L23a pseudogene), CNOT7(CCR4-NOT transcription complex, subunit 7), HOXC4(homeoboxC4), C8orf40(chromosome 8 open reading frame40), VWA5A(von Willebrand factor A domain containing 5A), INTS10(integrator complex subunit 10), PDPK1(3-phosphoinositide dependent protein kinase-1), BNIP3L(BCL2/adenovirus E1B 19kDa interacting protein 3-like), XK(X-linked Kx blood group (McLeod syndrome)), C9orf167(chromosome 9 open reading frame 167), PROSC(proline synthetase co-transcribed homolog (bacterial)), DDIT4(DNA-damage-inducible transcript 4), KLK12(kallikrein-related peptidase 12), LOC339352(cytosolic thiouridylase subunit 1 homolog (S. pombe) pseudogene), FDFT1(farnesyl-diphosphate farnesyl transferase1), GSTO2(glutathione S-transferase omega 2), ZNF185(zinc finger protein 185 (LIM domain)), SOX7(SRY-box containing gene 7), CTNNB1(catenin(cadherin-associated protein),beta1,88kDa), ARSD(arsenical resistance operon trans-acting repressor), TRIM29(tripartite motif containing 29), CCDC58(coiled-coil domain containing 58), DEFB1(defensin,beta1), FAM3D(family with sequence similarity 3, member D), GABRP(gamma-aminobutyric acid(GABA) A receptor,pi) 및 CA9(carbonic anhydrase IX)로 이루어진 군에서 선택되는 최소 1종의 유전자의 뉴클레오타이드 서열을 포함하는 세포에 분석하고자 하는 시료를 접촉시키는 단계; 및
상기 뉴클레오티드 서열의 발현량을 측정하는 단계를 더 포함하는, 위암의 림프절 전이의 억제 또는 예방용 물질의 스크리닝 방법.The method of claim 11, wherein HLA-DRB5 (major histocompatibility complex, class II, DR beta 5), DACH1 (dachshund homolog 1), IRX3 (iroquois homeobox 3), CD7 (CD7 antigen), YBX2 (HOXA11 antisense RNA), inositol-trisphosphate 3-kinase A (ITPKA), MHC class I polypeptide-related sequence B, ENO3 (enolase3, betamuscle), ARID3A (AT rich interactive domain 3A), LTB (lymphotoxinbeta) NINJ2 (ninjurin2), C20orf100 (TOX high mobility group box family member 2), NES (nestin), CENPN (centromere protein N), ARHGAP4 (RhoGTPase activating protein 4), FAM69B (family with sequence similarity 69, member B) (AFT-binding cassette), ABCB1 (ATP-binding cassette), KIFC1 (kinesin family member C1), RASAL3 (RAS protein activator like 3) (MDR / TAP), member 1), FOXA3 (forkheadboxA3), TEAD4 (TEA domain family member 4), CKS1B (CDC28 protein kinase regulatory subunit 1B), SLC39A8 ILO 39 (metal ion transporter), member 8), TNC (tenascin C), ELOVL5 (ELOVL fatty acid elongase 5), LOC730102 (quinone oxidoreductase- like protein 2 pseudogene), SLC26A6 (solute carrier family 26, member 6) aurora kinase A, intercellular adhesion molecule 3 (ICAM3), LOC729086 (vesicular overexpressed cancer, prosurvival protein 1 pseudogene), FYN (FYN oncogene related to SRC, FGR, YES), FLJ35776 (uncharacterized LOC649446) homology 2 domain-containing transforming protein D), BRI3BP (BRI3 binding protein), SLC37A4 (solute carrier family 37, member 4), INPP5E (inositol polyphosphate-5-phosphatase), HIST1H4H , H4h), GTF3A (general transcription factor IIIA), C13orf23 (proline and serine rich1), MLH1 (mutLhomolog1, coloncancer, nonpolyposistype2 (E. coli)), CD96 (CD96 antigen), GRTP1 (GH regulated TBC protein 1) (v-ets erythroblastosis virus E26 oncogenehomolog (avian)), FOXM1 (forkheadboxM1), TMEM156 (transmembrane protein 156), EXOSC8 exosome component 8), ZC3H3 (CG6694 gene product from transcript CG6694-RA), LOC646753 (ribosomal protein S26 pseudogene 2), ESPN (espin), FLOT1 (flotillin1), DTNA (dystrobrevin, alpha), SPTBN5 (cysteine-5), KBTBD12 (kelch repeat and BTB (POZ) domain containing 12), VARS2 (valyl-tRNA synthetase 2, mitochondrial (putative)), CD6 (CD6 antigen), CENPJ (centromere protein J), phosphatidylinositol glycan anchor biosynthesis class P), LOC440595 (eukaryotic translation elongation factor 1 alpha 1 pseudogene 11)), LOC653650 (3-phosphoinositide dependent protein kinase 1 pseudogene), BSPRY (B-box and SPRY domain containing), ALDH6A1 (aldehyde dehydrogenase 6 family , member A1), MRPL43 (mitochondrial ribosomal protein L43), C11orf74 (chromosome 11 open reading frame 74), PDCD2 (programmed cell death 2), RAC1 (ras-related C3 botulinum toxin substrate 1 ), PCM1 (pericentriolarmaterial1), HEPACAM2 (HEPACAM family member2), IFT20 (intraflagellar tra NKP3 (Nuclear RNA export factor 3), ABTB1 (ankyrin repeat and BTB (POZ)), EGFR2 (PTCA1), SDC1 (syndecan 1), EXTL3 (paclitaxel), and paclitaxel (paclitaxel) exostoses (multiple) -like 3), SLC38A10 (solute carrier family 38, member 10), ZNF395 (zinc finger protein 395), C17orf58 (chromosome 17 open reading frame 58), PTGFRN (prostaglandin F2 receptor negative regulator), WRB basic protein), EBP (emopamil binding protein (sterol isomerase)), C14orf4 (interferon regulatory factor 2 binding protein-like), TNFRSF10A (tumor necrosis factor receptor superfamily, member 10a) CCDC25 mirror-image polydactyly 1), AIG1 (androgen-induced 1), KCNK1 (potassium c (UBX domain protein 8), nuclear receptor interacting protein 1 (NRIP1), TRK-fusedgene, APPBP2 (cytoplasmic tail binding protein 2), IFT74 (intraflagellar transport 74 homolog (Chlamydomonas), DSG2 (desmoglein 2), ASMTL (acetyl serotonin O-methyl transferase-like), TMEM66 (transmembrane protein 66), C21orf33 (chromosome 21 open reading frame33), WDR23 (WD40repeat- (transketolase), SAV1 (salvador homolog 1 (Drosophila)), TMEM106B (transmembrane protein 106B), SLC25A6 (solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator, member 6), FUT6 (fucosyltransferase 6 (alpha (1,3) fucosyltransferase), LOC402251 (similar to Hypothetical protein MGC76216), DKFZp761P0423 (homolog of rat pragma of Rnd2), NEIL2 (nei endonuclease VIII- (Ribosomal protein S2 pseudogene), LOC651149 (similar to 60S ribosomal protein L3 (L4)), PPP2R2A (protein of the present invention), ICAM2 (intercellular adhesion molecule 2), DCAKD (dephospho-CoA kinase domain containing) phosphatase 2, regulatory subunit B, alpha), FLJ43681 (ribosomal protein L23a pseudogene), CNOT7 (CCR4-NOT transcription complex, subunit 7), HOXC4 (homeoboxC4), C8orf40 (chromosome 8 open reading frame40), VWA5A domain containing 5A), integrator complex subunit 10 (INTS10), 3-phosphoinositide dependent protein kinase-1 (PDPK1), BNIP3L (BCL2 / adenovirus E1B 19kDa interacting protein 3-like), XK (X-linked Kx blood group ), C9orf167 (chromosome 9 open reading frame 167), PROSC (proline synthetase co-transcribed homo (DNA-damage-inducible transcript 4), KLK12 (kallikrein-related peptidase 12), LOC339352 (cytosolic thiouridylase subunit 1 homolog (S. (glutathione S-transferase omega 2), ZNF185 (zinc finger protein 185 (LIM domain)), SOX7 (SRY-box containing gene 7), CTNNB1 (catenin cadherin-associated protein, beta1,88kDa), ARSD (arsenical resistance operon trans-acting repressor), TRIM29 (tripartite motif containing 29), CCDC58 (coiled-coil domain containing 58), DEFB1 (defensin, beta1), FAM3D analysis of cells containing nucleotide sequences of at least one gene selected from the group consisting of with sequence similarity 3, member D), GABRP (gamma-aminobutyric acid (GABA) A receptor, pi) and CA9 (carbonic anhydrase IX) Contacting the sample to be treated; And
And measuring the expression level of the nucleotide sequence. &Lt; Desc / Clms Page number 20 >