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 PDFInfo
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- 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
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- bladder cancer
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- 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
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- 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
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- 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-
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- 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.
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 |
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Application Number | Title | Priority Date | Filing Date |
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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)
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CN (1) | CN114150063A (fr) |
WO (1) | WO2023105297A2 (fr) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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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 |
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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 |
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2021
- 2021-12-09 CN CN202111497460.6A patent/CN114150063A/zh active Pending
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2022
- 2022-12-09 WO PCT/IB2022/020082 patent/WO2023105297A2/fr unknown
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Publication number | Publication date |
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WO2023105297A3 (fr) | 2023-08-03 |
CN114150063A (zh) | 2022-03-08 |
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