WO2023105297A2 - Marqueur de miarn dans l'urine pour le diagnostic du cancer de la vessie, réactif de diagnostic et kit - Google Patents

Marqueur de miarn dans l'urine pour le diagnostic du cancer de la vessie, réactif de diagnostic et kit Download PDF

Info

Publication number
WO2023105297A2
WO2023105297A2 PCT/IB2022/020082 IB2022020082W WO2023105297A2 WO 2023105297 A2 WO2023105297 A2 WO 2023105297A2 IB 2022020082 W IB2022020082 W IB 2022020082W WO 2023105297 A2 WO2023105297 A2 WO 2023105297A2
Authority
WO
WIPO (PCT)
Prior art keywords
mir
hsa
mirna
mirnas
bladder cancer
Prior art date
Application number
PCT/IB2022/020082
Other languages
English (en)
Chinese (zh)
Other versions
WO2023105297A3 (fr
Inventor
蒋贝尔
郭辉
张盼
陈阳
袁易初
杜晴晴
张楠
程赫
邹瑞阳
Original Assignee
觅瑞（杭州）生物科技有限公司
觅瑞实验室私人有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 觅瑞（杭州）生物科技有限公司, 觅瑞实验室私人有限公司 filed Critical 觅瑞（杭州）生物科技有限公司
Publication of WO2023105297A2 publication Critical patent/WO2023105297A2/fr
Publication of WO2023105297A3 publication Critical patent/WO2023105297A3/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA

Definitions

  • the urine miRNA marker when the urine miRNA marker is screened for any one or more of the 11 miRNAs in the above manner, it includes but is not limited to the following combinations: hsa-miR-143-3p>hsa-miR- 183-5p hsa-miR-101-3p hsa-miR-15b-5p hsa-miR-191-5p Instructions for hsa-miR-21-3p, hsa-miR-219a-5p, hsa-miR-3186-3p, hsa-miR-1-3p, hsa-miR-18a-3p, hsa-miR-205-5p; or hsa-miR-143-3p, hsa-miR-93-5p, hsa-miR-101-3p, hsa-miR-15b-5p, hsa-miR-21-3p, hsa-miR-219a
  • the urine miRNA marker is selected from one or more of the following six miRNAs: hsa-miR-143-3p, hsa-miR-183-5p, hsa-miR-21-3p , hsa-miR-219a-5p, hsa-miR-1-3p, hsa-miR-18a-3p o
  • the above is selected from hsa-miR-143-3p>hsa-miR-183-5p>hsa- miR-21-3p, hsa-miR-219a-5p > hsa-miR-l-3p ⁇ hsa-miR-18a-3p, at least 2 of these 6 miRNAs, the urinary miRNA markers, its AUC Values are higher than those of individual miRNAs such as hsa-miR-219a-5p or hsa-miR-1-3p.
  • the above is selected from hsa-miR-143-3p > hsa-miR-183-5p > hsa-miR-21-3p, hsa-miR-219a-5p > hsa-miR-1-3p > hsa-miR -18a-3p at least 5 of the 6 miRNAs, the urinary miRNA markers, the AUC value is higher than that of a single miRNA (such as hsa-miR-219a-5p or hsa-miR-1-3p).
  • the urine miRNA markers may be composed of the following six miRNAs: hsa-miR-143-3p, hsa-miR-183-5p, hsa-miR-21-3p, hsa- miR-219a-5p, hsa-miR-l-3p, Instructions hsa-miR-18a-3p o
  • the present invention also provides a diagnostic reagent for bladder cancer, including reagents for specifically detecting various urinary miRNA markers as described above.
  • the present invention also provides a diagnostic kit for bladder cancer, which includes various urinary miRNA markers as described above as standard products, and corresponding reagents for detecting various urinary miRNA markers as described above. primers.
  • the present invention also provides a method for early diagnosis and/or recurrence monitoring of bladder cancer using various urinary miRNA markers as described above, including the following steps: Step b Detecting the urine obtained from the subject the presence of miRNA in the sample; step 2, measuring the expression level of at least 1 miRNA in the miRNA markers in the urine sample; step 3, using the score based on the previously measured miRNA expression level to compare with the reference, by comparing the subjects Whether there is a significant difference between the sample and the reference sample for early diagnosis and/or recurrence monitoring of the possibility that the subject has bladder cancer.
  • the present invention provides various combinations of urinary miRNA markers, which are easy to operate, highly feasible, high in sensitivity and specificity, and have clinical diagnostic and guiding significance; moreover, the present invention can detect miRNA expression through urine , so as to achieve the purpose of non-invasive.
  • Figure 1 is a heat map of the expression levels of 16 (P ⁇ 0.05) differentially expressed bladder cancer miRNA diagnostic markers. miRNA expression levels (copy number/ml) are presented on a log2 scale and normalized to the zero mean. The color of the dots indicates the concentration. Hierarchical clustering was performed for two dimensions (miRNA and sample) based on Euclidean distance. For the horizontal dimension, color is used to represent case-control subjects.
  • Figure 2 is the AUC graph of bladder cancer miRNA diagnostic marker combinations in each cohort; among them, Figure 2-A is the AUC graph of 16 bladder cancer miRNA diagnostic marker combinations in each cohort, and Figure 2-B is 6 bladder cancer The AUC graph of miRNA diagnostic marker combinations in each cohort.
  • Figure 3 is a line box plot of the control and cancer prediction values of the six bladder cancer miRNA diagnostic marker combinations.
  • miRNA refers to microRNAs, ie small non-coding RNA molecules, which contain about 22 nucleotides in some embodiments, and exist in plants, animals and some viruses. miRNAs are known to have functions in RNA silencing and post-transcriptional regulation of gene expression. These highly conserved RNAs regulate gene expression by binding to the 3'-untranslated region (3'-UTR) of specific mRNAs. For example, each miRNA is thought to regulate multiple genes, and since hundreds of miRNA genes are predicted to exist in higher eukaryotes. miRNAs tend to be transcribed from several different loci in the genome.
  • 16 miRNA markers can detect bladder cancer with significant differences (p ⁇ 0.05): hsa-miR-374a-3p, hsa -miR-1 hsa-miR-183-5p>hsa-miR-93-5p>hsa-miR-101-3p>hsa-miR-15b-5p>hsa-mi hsa-miR-21-3p ⁇ hsa-miR -219a-5p hsa-miR-25-3p ⁇ hsa-miR-3186-3p ⁇ hsa-m hsa-miR-l-3p ⁇ hsa-miR-18a-3p ⁇ hsa-miR-205-5p>hsa-miR -425-3p; and, After screening, a combination of the 16 miRNA markers with a higher AUC value than the aforementioned, including hsa-miR-

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Hospice & Palliative Care (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention divulgue un marqueur de miARN dans l'urine pour le diagnostic du cancer de la vessie, un réactif de diagnostic et un kit. Le marqueur de miARN dans l'urine est sélectionné parmi un ou plusieurs des 16 miARN suivants : hsa-miR-374a-3p, hsa-miR-143-3p, hsa-miR-183-5p, hsa-miR-93-5p, hsa-miR-101-3p, hsa-miR-15b-5p, hsa-miR-191-5p, hsa-miR-21-3p, hsa-miR-219a-5p, hsa-miR-25-3p, hsa-miR-3186-3p, hsa-miR-454-3p, hsa-miR-1-3p, hsa-miR-18a-3p, hsa-miR-205-5p et hsa-miR-425-3p. La présente solution a une spécificité de population plus élevée ; et par comparaison avec d'autres marqueurs moléculaires de miARN, le présent marqueur de miARN est plus fiable.
PCT/IB2022/020082 2021-12-09 2022-12-09 Marqueur de miarn dans l'urine pour le diagnostic du cancer de la vessie, réactif de diagnostic et kit WO2023105297A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202111497460.6 2021-12-09
CN202111497460.6A CN114150063A (zh) 2021-12-09 2021-12-09 膀胱癌诊断用尿液miRNA标志物、诊断试剂及试剂盒

Publications (2)

Publication Number Publication Date
WO2023105297A2 true WO2023105297A2 (fr) 2023-06-15
WO2023105297A3 WO2023105297A3 (fr) 2023-08-03

Family

ID=80454142

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2022/020082 WO2023105297A2 (fr) 2021-12-09 2022-12-09 Marqueur de miarn dans l'urine pour le diagnostic du cancer de la vessie, réactif de diagnostic et kit

Country Status (2)

Country Link
CN (1) CN114150063A (fr)
WO (1) WO2023105297A2 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114150063A (zh) * 2021-12-09 2022-03-08 觅瑞（杭州）生物科技有限公司 膀胱癌诊断用尿液miRNA标志物、诊断试剂及试剂盒
ES2958840B2 (es) * 2022-07-19 2024-06-19 Fundacion Para La Investigacion Del Hospital Univ Y Politecnico La Fe De La Comunidad Valenciana Método de diagnóstico y estadificación de cáncer de vejiga basado en miRNAs

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103320504A (zh) * 2013-01-28 2013-09-25 深圳市人民医院 检测***物中microRNAs作为肺癌、结直肠癌和膀胱癌早期诊断生物标志
RO132683A2 (ro) * 2016-12-08 2018-06-29 Universitatea De Medicină Şi Farmacie "Iuliu Haţieganu"Din Cluj-Napoca Test de diagnostic molecular neinvaziv al cancerului de vezică ()
US20180258494A1 (en) * 2017-03-12 2018-09-13 Steven Goodison Materials and methods for bladder cancer detection
EP3492607A3 (fr) * 2017-11-30 2019-08-14 Università Degli Studi Di Torino Miarns urinaires pour le diagnostic in vitro du cancer de la vessie
KR102029775B1 (ko) * 2018-01-23 2019-10-08 충북대학교 산학협력단 비근침윤성 방광암 진단용 바이오마커 및 이의 용도
CN114269950A (zh) * 2019-08-19 2022-04-01 上海翔琼生物技术有限公司 检测膀胱及泌尿道上皮癌的尿液小rna指纹图谱及其应用
CN114150063A (zh) * 2021-12-09 2022-03-08 觅瑞（杭州）生物科技有限公司 膀胱癌诊断用尿液miRNA标志物、诊断试剂及试剂盒

Also Published As

Publication number Publication date
WO2023105297A3 (fr) 2023-08-03
CN114150063A (zh) 2022-03-08

Similar Documents

Publication Publication Date Title
WO2023105297A2 (fr) Marqueur de miarn dans l'urine pour le diagnostic du cancer de la vessie, réactif de diagnostic et kit
JP2015128442A (ja) 早期結腸直腸癌の検出のための血漿マイクロｒｎａ
CN108949992B (zh) 一种与食管鳞癌及其分级相关的生物标志物
CN108676872B (zh) 一种与哮喘相关的生物标志物及其应用
CN106676191B (zh) 一种用于结肠腺癌的分子标志物
CN109055555B (zh) 一种肺癌早期转移诊断标志物及其试剂盒和应用
WO2017223216A1 (fr) Compositions et procédés de diagnostic de cancers du poumon à l'aide de profils d'expression génique
CN111187840B (zh) 一种用于早期乳腺癌诊断的生物标志物
WO2018219264A1 (fr) Utilisation d'un arn non codant à chaîne longue comme marqueur de molécule du cancer de la prostate
Li et al. Expression alteration of long non-coding RNAs and their target genes in the intestinal mucosa of patients with Crohn’s disease
CN110229899B (zh) 用于结直肠癌早期诊断或预后预测的血浆标记物组合
KR102096498B1 (ko) 대장암 진단 또는 재발 예측을 위한 마이크로RNA-4732-5p 및 이의 용도
WO2023105296A2 (fr) Marqueur de miarn dans l'urine pour le diagnostic du cancer de la prostate, réactif de diagnostic et kit
WO2023105295A2 (fr) Marqueur de miarn dans l'urine pour le diagnostic du cancer du rein, réactif de diagnostic et kit
CN111424085B (zh) tRNA来源片段在制备乳腺癌诊断试剂中的应用
CN107299129B (zh) 循环核酸作为乳腺癌生物标志物的应用
TWI829042B (zh) 泛癌症早篩預測方法
CN110592219B (zh) 一种用于乳腺癌的lncRNA诊治标志物
US20150329911A1 (en) Nucleic acid biomarkers for prostate cancer
CN114107514A (zh) 一种用于结直肠癌诊断的miRNA分子标志物及其试剂盒
KR102096499B1 (ko) 대장암 진단 또는 재발 예측을 위한 마이크로rna-3960 및 이의 용도
CN108998528B (zh) 肺癌诊断分子标记物lncRNA LINC00516和试剂盒及其应用
CN118434885A (zh) 膀胱癌癌诊断用尿液miRNA标志物、诊断试剂及试剂盒
CN118414427A (zh) ***癌诊断用尿液miRNA标志物、诊断试剂及试剂盒
WO2024047914A1 (fr) Procédé d'analyse, kit et dispositif de détection pour le diagnostic du cancer au moyen de l'expression de microarn

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22903654

Country of ref document: EP

Kind code of ref document: A2