基于生物信息学的胃肠道癌症差异甲基化-差异表达基因联合筛选分析

Combined Screening Analysis of Differentially Methylated and Differentially Expressed Genes in Gastrointestinal Cancer Based on Bioinformatics

背景:胃肠道癌症的发生、发展是多基因参与、多因素作用的结果。DNA甲基化是重要的表观遗传调控方式之一,对胃肠道癌症的诊断和治疗具有重要作用。目的:利用生物信息学分析方法,筛选并验证胃肠道癌症共同的差异甲基化-差异表达基因,为解析DNA甲基化在胃肠道癌症发生、发展中的分子机制提供理论依据。方法:选取GEO数据库中表达谱芯片和甲基化芯片数据,应用GEO2R筛选胃肠道癌症共同的差异甲基化-差异表达基因,STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,筛选出核心基因,行GO分析和KEGG分析,并应用TCGA数据库进行验证。结果:共筛选出胃肠道癌症60个高甲基化-低表达基因(Hyper-LGs)和407个低甲基化-高表达基因(Hypo-HGs)。GO分析示Hyper-LGs涉及46个功能,Hypo-HGs涉及164个功能。KEGG分析示Hyper-LGs主要富集于Rap1信号通路、吗啡成瘾通路等,而Hypo-HGs主要富集于ECM-受体相互作用信号通路、细胞周期通路、PI3K-Akt信号通路等。TCGA数据库验证结果显示,CDH2为胃肠道癌症共同的Hyper-LGs,EXO1为共同的Hypo-HGs。结论:基于生物信息学的差异甲基化-差异表达基因联合筛选分析可为阐明DNA甲基化在胃肠道癌症发生、发展中的表观遗传学作用提供新的线索,有助于全面解析胃肠道癌症DNA甲基化调控的作用及其机制,为胃肠道癌症诊断标志物的筛选和药物治疗精准靶点的选择提供理论基础。

Background:The occurrence and development of gastrointestinal cancer are the result of multi-genes and multi-factors.DNA methylation is one of the important ways of epigenetic regulation,which plays an important role in the diagnosis and treatment of gastrointestinal cancer.Aims:To screen and verify the differentially methylated and differentially expressed genes in gastrointestinal cancer by bioinformatics analysis,and to provide a theoretical basis for the analysis of molecular mechanism of DNA methylation in the occurrence and development of gastrointestinal cancer.Methods:Data from the expression profile chip and methylation chip in the GEO database were selected.Differentially methylated and differentially expressed genes in gastrointestinal cancer were screened by using GEO2R.STRING database was used to construct protein-protein interaction(PPI)network,and the core genes were screened and analyzed by GO analysis and KEGG analysis,and were verified by TCGA database.Results:Sixty high methylation-low expression genes(Hyper-LGs)and 407 low methylation-high expression genes(Hypo-HGs)were obtained.GO analysis showed that Hyper-LGs involved 46 functions and Hypo-HGs involved 164 functions.KEGG analysis showed that Hyper-LGs were mainly enriched in Rap1 signaling pathway,and morphine addiction pathway,while Hypo-HGs were mainly enriched in ECM-receptor interaction,cell cycle,PI3K-Akt signaling pathway.TCGA database results showed that CDH2 was the common Hyper-LGs in gastrointestinal cancer,and EXO1 was the common Hypo-HGs.Conclusions:Bioinformatics-based combined screening analysis of differentially methylated and differentially expressed genes in gastrointestinal cancer provides new clues for elucidating the epigenetic role of DNA methylation in the development of gastrointestinal cancer,which is helpful for comprehensively exploring the role and mechanism of DNA methylation regulation in gastrointestinal cancer,and can provide a theoretical basis for the screening of diagnostic markers of gastrointestinal cancer and the selection of precise targets for drug therapy.