CN104593500B - Y染色体中特异性甲基化位点作为癌症诊断标志物的应用 - Google Patents

Y染色体中特异性甲基化位点作为癌症诊断标志物的应用 Download PDF

Info

Publication number
CN104593500B
CN104593500B CN201510027708.0A CN201510027708A CN104593500B CN 104593500 B CN104593500 B CN 104593500B CN 201510027708 A CN201510027708 A CN 201510027708A CN 104593500 B CN104593500 B CN 104593500B
Authority
CN
China
Prior art keywords
cancer
methylation
chromosome
screening
sites
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
CN201510027708.0A
Other languages
English (en)
Other versions
CN104593500A (zh
Inventor
孙英丽
姚鲁帅
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
WUXI SHENRUI BIO-PHARMACEUTICALS Co.,Ltd.
Original Assignee
Beijing Institute of Genomics of CAS
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 Beijing Institute of Genomics of CAS filed Critical Beijing Institute of Genomics of CAS
Priority to CN201510027708.0A priority Critical patent/CN104593500B/zh
Publication of CN104593500A publication Critical patent/CN104593500A/zh
Priority to US15/544,735 priority patent/US10648039B2/en
Priority to EP15878635.0A priority patent/EP3249051B1/en
Priority to JP2017538949A priority patent/JP6606554B2/ja
Priority to KR1020177021536A priority patent/KR102067607B1/ko
Priority to PCT/CN2015/099922 priority patent/WO2016115967A1/zh
Application granted granted Critical
Publication of CN104593500B publication Critical patent/CN104593500B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • 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
    • C12Q1/6809—Methods for determination or identification of nucleic acids involving differential detection
    • 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
    • C12Q1/6869—Methods for sequencing
    • C12Q1/6872—Methods for sequencing involving mass spectrometry
    • 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
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • 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
    • C12Q2600/118—Prognosis of disease development
    • 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
    • C12Q2600/136—Screening for pharmacological compounds
    • 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
    • C12Q2600/154—Methylation 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
    • C12Q2600/158—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
    • C12Q2600/16—Primer sets for multiplex assays

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Pathology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Hospice & Palliative Care (AREA)
  • Medicinal Chemistry (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

本发明涉及一种癌症早期诊断的方法，具体涉及一种Y染色体特异性甲基化位点的筛选方法，所述方法包括：a)获取患者样本，b)从a)步骤获得的样本提取DNA，c)确定样本的全基因组甲基化水平，d)分析Y染色体甲基化信息，e)筛选甲基化保守位点，f)筛选具有明显差异的甲基化位点，g)筛选具有明显差异的甲基化保守位点。本发明还涉及通过上述筛选方法获得的癌症诊断标志物，以及其在制备癌症早期诊断、预测癌症发生风险的试剂或试剂盒中的用途，优选地，上述癌症为前列腺癌。

Description

Y染色体中特异性甲基化位点作为癌症诊断标志物的应用
技术领域
本发明涉及生物技术领域，具体涉及一种作为癌症诊断标志物的Y染色体中特异甲基化位点及其应用。
背景技术
DNA甲基化是一种常见的表观遗传(epigenetic)修饰，在DNA甲基转移酶催化下，利用S－腺苷甲硫氨酸提供的甲基，将胞嘧啶的第5位碳原子甲基化，从而使胞嘧啶转化为5－甲基胞嘧啶，其对基因的表达调控有着至关重要的作用。
癌症，又被称为恶性肿瘤，是由控制细胞生长增殖机制的失常而引起的疾病。正常情况下，细胞的生长增殖由包括癌基因和抑癌基因在内的一些调控生长发育的基因严密调控，保持正常的生理状态；在受到辐射，化学污染，病毒感染以及内分泌失衡等多种因素的影响下，导致体内癌基因的激活以及抑癌基因的失活，从而导致的癌症的发生。除了基因突变之外，表观遗传如组蛋白修饰、DNA甲基化等异常调节也在肿瘤的发生发发展过程中起着重要的作用。在多种癌症中均有发现表观修饰的异常。总之，肿瘤的发生时一个极其复杂的过程，是由于体内癌基因、抑癌基因以及表观修饰等异常调节并积累的结果。
DNA甲基化与癌症的发生有着密切的关系，在许多癌症中都发现存在DNA甲基化异常的现象。DNA甲基化具有一定的稳定性，它是癌症发生中的早期事件。近年来许多研究证明，DNA的甲基化异常可以作为一种癌症诊断的生物标志物。目前，许多特定基因启动子区的DNA甲基化异常被用来作为前列腺癌诊断的一种潜在标志物。
目前前列腺癌的主要诊断方法是直肠诊断、血清PSA、组织免疫切片等，其中组织免疫切片是前列腺癌的黄金诊断方法，但是由于其要首先获得病人的前列腺组织，给病人带来较大的痛苦，不太适合前期诊断。PSA是目前用于前列腺癌前期诊断的一种标志物，但是其检测并不是十分精确，存在一定的灰区。所以寻找一种方便准确的诊断标志物对于前列腺癌的早期诊断十分迫切。
现有技术中，存在各种针对DNA甲基化监测的方法，比如CN104062334A所公开的一种针对DNA甲基化监测的定量分析方法，再比如DNA甲基化芯片技术。但是，现阶段在检测甲基化是否异常时缺乏一个统一的、较为准确的标准，无法通过特定位点甲基化水平的变化以尽早预测患有癌症的风险。
发明内容
本发明的目的是提供一种癌症早期诊断的方法。
为了达到上述目的，本发明提供一种利用检测Y染色体特定甲基化位点甲基化水平的变化情况来辅助诊断癌症的方法。
本发明人通过癌旁间以及癌旁和癌间分别对比，找出了特定的甲基化位点，即在癌旁中个体间差异很小而在癌中具有明显差异的甲基化位点，并以该位点在癌旁中的平均甲基化水平作为验证标准，对比待检测病人的该位点甲基化水平，观察是否发生异常，来判断病人是否具有患有前列腺癌的风险。
具体地，首先从癌旁样本中筛选出相对保守的甲基化位点；然后再根据癌组织和癌旁组织进行对比，找出具有明显差异的位点；最后筛选出具有明显差异的保守性甲基化位点，即可作为潜在的诊断标志物。
所述保守性甲基化位点为癌旁样本间SD值小于等于0.25的点；所述明显差异为癌组织和癌旁组织甲基化水平差值的绝对值大于等于0.2，p值小于等于0.01。
因此，在本发明的一个方面，本发明提供一种Y染色体特异性甲基化位点，该位点的甲基化水平的突变可以作为前列腺癌诊断的新的靶点。
在另一个方面，本发明提供一种Y染色体特异性甲基化位点的筛选方法，所述方法包括：a)获取患者样本，b)从a)步骤获得的样本提取DNA，c)确定样本的全基因组甲基化水平，d)分析Y染色体甲基化信息，e)筛选甲基化保守位点，f)筛选具有明显差异的甲基化位点，g)筛选具有明显差异的甲基化保守位点。
优选地，所述样本为癌组织和癌旁组织。所述癌组织优选为前列腺癌组织。
优选地，所述甲基化保守位点为在癌旁组织中样本间标准方差SD值小于等于0.25的点。
优选地，所述明显差异为甲基化水平变化在0.2及以上，且p值和q值均小于等于0.01。可选地，所述变化为升高或降低。
优选地，所述具有明显差异的甲基化保守位点为癌旁样本间标准方差SD值在0.25以内且在癌组织中甲基化水平升高或降低了0.2及以上水平的点。
在又一个方面，本发明提供了一种癌症诊断标志物，所述标志物由Y染色体中特异性甲基化位点组成，所述位点通过上述方法筛选得到。
具体地，所述癌症诊断标志物包括cg03052502、cg04462340、cg05163709、cg05544622、cg14466580和cg27539893。
在另一个方面，本发明提供了一种癌症诊断标志物在制备癌症早期诊断的试剂中的用途。优选地，所述癌症为前列腺癌。
在另一个方面，本发明提供了一种癌症诊断标志物在制备预测癌症发生风险的试剂中的用途。优选地，所述癌症为前列腺癌。
在另一个方面，本发明提供了一种早期诊断癌症的试剂盒。优选地，所述癌症为前列腺癌。
有益效果：
本发明提供了一种有效筛选癌症诊断标志物的方法，并提供了较为准确的筛选标准，拓展了癌症临床检测的途径，所筛选出的特异性位点可以有效用于癌症的早期快速诊断。
附图说明
图1为癌旁组织中筛选出的75个保守位点的甲基化水平热图。
图2为癌组织和癌旁组织对比筛选出的37个具有明显变化的甲基化位点。
图3为在75个癌旁组织中保守的位点，6个在癌组织中发生了明显的变化。
图4为筛选出的最终的6个位点的甲基化水平(上图)，以及每个位点在66例癌组织中发生明显变化的比例(下图，黑色标记代表明显变化)。
具体实施方式
以下实施例用于举例说明本发明，其并不用于限制本发明。
实施例1 癌组织及癌旁组织的收集鉴定
从病人癌症切割手术中搜集组织，并经具有丰富经验的医师通过组织免疫切片将癌组织和癌旁组织区分对应收集。
实施例2保守甲基化位点的筛选
搜集获取66例前列腺癌病人的癌旁组织，并从中提取DNA。利用DNA甲基化芯片测得66例样本的全基因组甲基化水平，分取其中Y染色体甲基化信息分析对比，根据样本间的SD值筛选出甲基化保守位点(SD值≤0.25)。结果参见图1。
实施例3 明显差异的甲基化位点的筛选
利用Illumina Methylation Analyzer(IMA)软件包，根据66对癌组织和癌旁组织间的Y染色体上DNA甲基化水平比对，筛选出在癌组织中具有明显变化的DNA甲基化位点(甲基化水平变化β≥0.2，p值≤0.01)。
实施例4 筛选出发生明显变化的保守性位点
根据实施例2和实施例3中的结果，筛选出两者的交集(即在癌旁组织中保守而在癌组织中发生明显变化的甲基化位点)，共6个位点(见图3)，并且将这6个位点在每一对癌-癌旁中对比检测，计算出有多少比例的癌中确实发生了明显的甲基化变化(见图4)。这些交集位点即在癌中发生明显甲基化水平变化的保守位点，可以作为前列腺癌诊断的标志物。
以上所述仅为本发明的优选实施例而已，并不用于限制本发明，对于本领域的技术人员来说，本发明可以有各种更改和变化。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (1)

1.一种试剂盒，其特征在于，所述试剂盒用于前列腺癌早期诊断和/或前列腺癌患病风险预测；所述试剂盒包括检测Y染色体特异性甲基化位点的甲基化水平的试剂，其中所述Y染色体特异性甲基化位点包括cg03052502、cg04462340、cg05163709、cg05544622、cg14466580和cg27539833。
CN201510027708.0A 2015-01-20 2015-01-20 Y染色体中特异性甲基化位点作为癌症诊断标志物的应用 Active CN104593500B (zh)

Priority Applications (6)

Application Number Priority Date Filing Date Title
CN201510027708.0A CN104593500B (zh) 2015-01-20 2015-01-20 Y染色体中特异性甲基化位点作为癌症诊断标志物的应用
US15/544,735 US10648039B2 (en) 2015-01-20 2015-12-30 Use of methylation sites in Y chromosome as prostate cancer diagnosis marker
EP15878635.0A EP3249051B1 (en) 2015-01-20 2015-12-30 Use of methylation sites in y chromosome as prostate cancer diagnosis marker
JP2017538949A JP6606554B2 (ja) 2015-01-20 2015-12-30 Ｙ染色体のメチル化部位を前立腺ガンの診断用マーカとする使用
KR1020177021536A KR102067607B1 (ko) 2015-01-20 2015-12-30 Y 염색체 메틸화 사이트의 전립선암 진단 마커로써의 응용
PCT/CN2015/099922 WO2016115967A1 (zh) 2015-01-20 2015-12-30 Y染色体甲基化位点作为前列腺癌诊断标志物的应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510027708.0A CN104593500B (zh) 2015-01-20 2015-01-20 Y染色体中特异性甲基化位点作为癌症诊断标志物的应用

Publications (2)

Publication Number Publication Date
CN104593500A CN104593500A (zh) 2015-05-06
CN104593500B true CN104593500B (zh) 2017-02-22

Family

ID=53119551

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510027708.0A Active CN104593500B (zh) 2015-01-20 2015-01-20 Y染色体中特异性甲基化位点作为癌症诊断标志物的应用

Country Status (6)

Country Link
US (1) US10648039B2 (zh)
EP (1) EP3249051B1 (zh)
JP (1) JP6606554B2 (zh)
KR (1) KR102067607B1 (zh)
CN (1) CN104593500B (zh)
WO (1) WO2016115967A1 (zh)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107190076B (zh) * 2017-06-28 2019-12-27 中国科学院苏州生物医学工程技术研究所 一种人肿瘤相关的甲基化位点及其筛选方法和用途
CN107604061B (zh) * 2017-08-31 2021-02-02 中国科学院北京基因组研究所 线粒体-细胞核dna甲基化联合位点的筛选方法和应用
CN108531593A (zh) * 2018-04-17 2018-09-14 中国科学院北京基因组研究所 特异甲基化位点作为乳腺癌复发诊断标志物的应用
CN108300787A (zh) * 2018-04-17 2018-07-20 中国科学院北京基因组研究所 特异甲基化位点作为乳腺癌早期诊断标志物的应用
CN108676879A (zh) * 2018-05-24 2018-10-19 中国科学院北京基因组研究所 特异甲基化位点作为乳腺癌分子分型诊断标志物的应用
CN108796062A (zh) * 2018-06-06 2018-11-13 无锡正则精准医学检验有限公司 一种检测tgfbi基因多态性的试剂盒
CN112877419A (zh) * 2021-01-20 2021-06-01 武汉大学 预测精神分裂症发生风险的dna甲基化标记物及筛选方法和应用
CN112779334B (zh) * 2021-02-01 2022-05-27 杭州医学院 一种用于前列腺癌早期筛查的甲基化标志物组合及筛选方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL186980A0 (en) 2006-10-31 2008-02-09 Veridex Llc Characterizing prostate cancer
US20080254455A1 (en) 2007-04-12 2008-10-16 Haiying Wang Detecting prostate cancer
US20140315192A1 (en) 2013-03-06 2014-10-23 Veridex, Llc Characterizing Prostate Cancer
WO2014160829A2 (en) * 2013-03-28 2014-10-02 Wisconsin Alumni Research Foundation Unbiased dna methylation markers define an extensive field defect in histologically normal porstate tissues associated with prostate cancer: new biomarkers for men with prostate cancer

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Deletion, Methylation, and Expression of the NKX3.1 Suppressor Gene in Primary Human Prostate Cancer;Asatiani e et al;《Cancer Res》;20050215;第65卷;1164 *
Factor interaction analysis for chromosome 8 and DNA methylation alterations highlights innate immune response suppression and cytoskeletal changes in prostate cancer;Schulz WA et al;《Molecular Cancer》;20070205;第6卷;14 *
癌表观遗传调控与癌症治疗;刘志坚等;《中国生物化学与分子生物学报》;20110430;第27卷(第4期);310-315 *

Also Published As

Publication number Publication date
US20170362663A1 (en) 2017-12-21
CN104593500A (zh) 2015-05-06
WO2016115967A1 (zh) 2016-07-28
EP3249051A1 (en) 2017-11-29
JP6606554B2 (ja) 2019-11-13
KR20170100029A (ko) 2017-09-01
EP3249051A4 (en) 2018-09-26
US10648039B2 (en) 2020-05-12
EP3249051B1 (en) 2021-01-13
KR102067607B1 (ko) 2020-01-20
JP2018504906A (ja) 2018-02-22

Similar Documents

Publication Publication Date Title
CN104593500B (zh) Y染色体中特异性甲基化位点作为癌症诊断标志物的应用
Straub et al. Ureterorenoscopic biopsy and urinary cytology according to the 2004 WHO classification underestimate tumor grading in upper urinary tract urothelial carcinoma
CN105018594A (zh) 一种结直肠癌早期诊断标记物及相关试剂盒
CN105316421A (zh) 用于检测与肺癌相关的shox2基因启动子区甲基化程度的试剂盒
CN111378754B (zh) 基于tcga数据库的乳腺癌甲基化生物标志物及其筛选方法
CN110452981A (zh) 基于外周血的肺癌早筛用的试剂盒
CN108300787A (zh) 特异甲基化位点作为乳腺癌早期诊断标志物的应用
CN107326065A (zh) 一种基因标识物的筛选方法及其应用
CN105779435A (zh) 试剂盒及其用途
CN115851951A (zh) 含多组学标志物组合物的早期肝癌检测模型构建及试剂盒
Yu et al. Urinary and plasma cell-free DNA comparison for lung cancer patients treated with epidermal growth factor receptor—thyroxine kinase inhibitors
CN104450702B (zh) 一种血清miRNA生物标志物组合物与应用
CN112063714A (zh) 一种与结直肠癌相关的miRNA及其应用
CN105779433A (zh) 试剂盒及其用途
CN107604061B (zh) 线粒体-细胞核dna甲基化联合位点的筛选方法和应用
CN108060231A (zh) 用于宫颈癌基因FAM19A4、miR-124-2甲基化检测的引物对、试剂盒及方法
CN111778335A (zh) 用于检测胰腺癌的癌组织和癌旁组织的tsRNA标志物、探针及其应用
CN105018585B (zh) 一种预测甲状腺肿瘤良恶性的试剂盒
CN116189904A (zh) 一种分化型甲状腺癌的基因甲基化诊断模型及其构建方法
CN107119144A (zh) 多功能转录调控因子ctcf的dna结合位点ctcf_55的应用
CN106367526A (zh) 一种诊断前列腺癌的产品及其应用
CN106367509A (zh) Loc100128675作为检测前列腺癌的分子标记物及其在诊断试剂盒中的应用
CN106282366A (zh) 一种与前列腺癌相关的分子标记物及其应用
CN105950723A (zh) 用于结直肠癌早期诊断的无创甲基化定量检测试剂盒
CN106148511A (zh) 一种肝癌患者接受切除术后复发风险的预测标志物及试剂盒

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CP01 Change in the name or title of a patent holder
CP01 Change in the name or title of a patent holder

Address after: 100101 Beijing Institute of genomics, Chinese Academy of Sciences

Patentee after: Beijing Institute of genomics, Chinese Academy of Sciences

Address before: 100101 Beijing Institute of genomics, Chinese Academy of Sciences

Patentee before: BEIJING INSTITUTE OF GENOMICS, CHINESE ACADEMY OF SCIENCES

TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20211215

Address after: 5 / F, c30303, C5, area C, Wuxi Huishan life science and Technology Industrial Park, 1699 Huishan Avenue, Huishan District, Wuxi City, Jiangsu Province, 214000

Patentee after: WUXI SHENRUI BIO-PHARMACEUTICALS Co.,Ltd.

Address before: 100101 Beijing Institute of genomics, Chinese Academy of Sciences

Patentee before: Beijing Institute of genomics, Chinese Academy of Sciences

PE01 Entry into force of the registration of the contract for pledge of patent right
PE01 Entry into force of the registration of the contract for pledge of patent right

Denomination of invention: Application of Specific Methylation Sites on the Y Chromosome as Cancer Diagnostic Markers

Effective date of registration: 20230925

Granted publication date: 20170222

Pledgee: Agricultural Bank of China Limited by Share Ltd. Wuxi Huishan branch

Pledgor: WUXI SHENRUI BIO-PHARMACEUTICALS Co.,Ltd.

Registration number: Y2023980058229