应用基因芯片技术筛选结直肠癌中差异DNA甲基化位点  

Screening of Differential DNA Methylation Loci in Colorectal Cancer by Gene Microarray Technique

作　　者：余捷[1] 王梓桦 杨世英[1] 薛寒冰[1] YU Jie;WANG Zihua;YANG Shiying;XUE Hanbing(Division of Gastroenterology and Hepatology,Renji Hospital,School of Medicine,Shanghai Jiao Tong University;Shanghai Institute of Digestive Disease,Shanghai(200001))

机构地区：[1]上海交通大学医学院附属仁济医院消化内科,上海市消化疾病研究所,200001

出　　处：《胃肠病学》2018年第6期330-335,共6页Chinese Journal of Gastroenterology

基　　金：上海市科学技术委员会(15DZ1940202)

摘　　要：背景:DNA甲基化作为表观遗传学修饰的重要组成部分,与结直肠癌等多种肿瘤的发生、发展密切相关,但具体作用机制尚未完全明确。筛选特异性甲基化基因和构建肿瘤的甲基化表达谱已成为当前研究热点。目的:应用基因甲基化芯片技术初步筛选结直肠癌组织与癌旁正常黏膜组织间差异甲基化位点,构建特异性结直肠癌差异甲基化基因谱。方法:应用甲基化450K芯片技术对6例结直肠癌及其癌旁组织进行甲基化分析,共分析位点431 467个,按P值筛选出异常甲基化位点,按甲基化β值差值区分高甲基化位点和低甲基化位点;对筛选出的差异甲基化位点进一步行GO分析和KEGG分析,了解差异甲基化位点的功能。结果:共检出结直肠癌和癌旁正常组织显著差异的甲基化位点3 649个,其中高甲基化位点1 259个,主要分布于基因启动子区和基因体,筛选出特异的SLC15A3等高甲基化基因;低甲基化位点共2 390个,主要分布于基因间区和基因体,筛选出特异的ACOT2、TTLL8、UHRF1等低甲基化基因。GO分析和KEGG分析发现,这些基因功能与DNA结合、转录因子活性、信号转导通路等有关。结论:结直肠癌和癌旁正常组织存在大量差异甲基化位点,提示DNA异常甲基化与结直肠癌的发生、发展密切相关。基因芯片技术可用于结直肠癌差异甲基化位点的初筛,但构建结直肠癌差异甲基化谱作为临床分子标记物仍需行进一步验证。Background:DNA methylation is a vital part of epigenetic modification,and is closely related with the development and progress of multiple tumors such as colorectal cancer.However,its mechanism is not fully clarified.Screening specific methylation gene and construct the methylation expression profile of tumor has become the current research hotspot.Aims:To screen the differential methylation loci in colorectal cancer and para-cancerous normal tissue by gene methylation microarray technique,and to construct specific differential methylation gene profile of colorectal cancer.Methods:Methylation 450K bead-chip was applied to detect the methylation status in colorectal cancer and para-cancerous normal tissues of 6 cases.A total of 431 467 loci were analyzed and compared.Aberrant methylation loci were screened according to P value,and the hypermethylation loci and hypomethylation loci were differentiated by delta beta value.Moreover,the function of differential methylation gene was further analyzed by GO analysis and KEGG analysis.Results:A total of 3 649 differential methylation loci were found by comparing colorectal cancer tissue and para-cancerous normal tissue,including 1 259 hypermethylation loci,which mainly located in promoter and genosome,and 2 390 hypomethylation loci,which mainly located in intergenic region and genosome.A panel of aberrant methylation gene loci was screened out,including hypermethylation gene loci such as SLC15A3 and hypomethylation gene loci such as ACOT2,TTLL8 and UHRF1.GO analysis and KEGG analysis showed that the function of these genes might be correlated with DNA binding,transcription factor activity and signal transduction pathway.Conclusions:There are many differential methylation loci in colorectal cancer and para-cancerous normal tissues,suggesting that aberrant DNA methylation is closely related with the development and progress of colorectal cancer.DNA methylation microarray technique could be applied for preliminary screening of differential methylation loci.However,constructi

关 键 词：DNA甲基化 结直肠肿瘤 芯片分析技术 

分 类 号：R735.34[医药卫生—肿瘤]