与胃癌发病相关的核心基因筛选及生物学功能分析  

Screening and biological function analysis of hub genes related to gastric cancer

作　　者：宋思源 温芳 黄雯洁 陈晓雪 阮帅 顾苏平 顾培杏 周佳钰 李烨 刘佳彤 舒鹏 SONG Siyuan;WEN Fang;HUANG Wenjie;CHEN Xiaoxue;RUAN Shuai;GU Suping;GU Peixing;ZHOUJiayu;LI Ye;LIU Jiatong;SHU Peng(Department of Oncology,Affiliated Hospital of Nanjing University of Traditional Chinese Medicine,Nanjing 210029,China;不详)

机构地区：[1]南京中医药大学附属医院肿瘤内科,南京210029 [2]南京中医药大学 [3]江苏省中医院肿瘤内科

出　　处：《山东医药》2021年第30期1-5,共5页Shandong Medical Journal

基　　金：国家自然科学基金面上项目(81673918);国家中医药管理局重大疑难疾病中西医临床协作试点胃癌项目;国家中医药管理局《中医药循证能力建设项目》(2019XZZX-ZL003);南京中医药大学中医学优势学科三期项目开放课题(ZYX03KF020);江苏省中医药管理局科技项目(ZD201803)。

摘　　要：目的运用生物信息学方法筛选与胃癌发病相关的核心基因,并分析其生物学功能。方法①胃癌患者癌组织及健康成人胃组织中表达上调的低甲基化基因、表达上调的低甲基化(致)癌基因、表达下调的高甲基化基因及表达下调的高甲基化抑癌基因筛选:从基因表达综合数据库中提取基因表达微阵列GSE118916、基因甲基化微阵列GSE25869。通过limma软件包和维恩图筛选胃癌患者及健康成年患者胃组织的差异表达基因和差异表达甲基化基因。从癌基因数据库和肿瘤抑制基因数据库中筛选胃癌的致癌基因和抑癌基因,绘制Venn图筛选得到表达上调的低甲基化基因、表达上调的低甲基化(致)癌基因、表达下调的高甲基化基因及表达下调的高甲基化抑癌基因。②胃癌患者癌组织表达上调的低甲基化基因、表达下调的高甲基化基因的主要基因筛选及生物学功能分析:采用DAVID数据库对表达上调的低甲基化基因、表达下调的高甲基化基因进行基因本体论(GO)分析和基因组百科全书(KEEG)通路富集分析。并导入String数据库,构建蛋白质—蛋白质相互作用网络图,分析蛋白质网络相互作用的主要基因。③胃癌发病的核心基因筛选及验证:采用GEPIA、Oncomine、HPA和cBioPortal数据库从表达上调的低甲基化基因、表达上调的低甲基化(致)癌基因、表达下调的高甲基化基因及表达下调的高甲基化抑癌基因中筛选出与胃癌发病相关的核心基因。并对核心基因进行GO及KEGG富集分析。结果①胃癌患者癌组织中有FN1、COL3A1及COL1A1等110个表达上调的低甲基化基因,其中TAC1、TWIST1、UCHL1、SPARC、GREM1、MEF2C、MAFB等9个基因为表达上调的低甲基化(致)癌基因;有CDH1、FOXA1及KLF4等23个表达下调的高甲基化基因,其中AZGP1、CDH1为表达下调的高甲基化抑癌基因。②表达上调的低甲基化基因的生物过程主要涉及细�Objective The hub genes related to gastric cancer(GC)were screened by bioinformatics and their biological functions were analyzed.Methods①Screening of high-regulated hypomethylated genes(Hypo-HGs),up-regulated hypomethylated oncogenes,low-regulated hypermethylated genes(Hyper-LGs)and down-regulated hypermethylated tumor suppressor genes(TSGs)in GC tissues of patients and healthy adults:Gene expression microarray GSE118916 and gene methylation microarray GSE25869 were extracted from the comprehensive database of gene expression(GEO).We screened differentially expressed genes(DEGs)and differentially expressed methylated genes(DMGs)in the gastric tissues of patients with GC and healthy adults by limma software package and venn diagram.The oncogenes and TSGs of GC were screened from oncogene database and tumor suppressor gene database,and the Hypo-HGs,up-regulated hypomethylation oncogenes,Hyper-LGs and TSGs were screened by drawing Venn diagram.②Main gene screening and biological function analysis of Hypo-HGs and Hyper-LGs in the cancer tissues of patients with GC:Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes Genomes(KEGG)enrichment analysis were carried out on Hypo-HGs and Hyper-LGs by using DAVID database.And then we imported them to the String database,built the network diagram of protein-protein interaction(PPI),and analyzed the main genes of network interaction in protein.③Screening and verification of hub genes of GC:GEPIA,Oncomine,HPA and cBioPortal databases were used to screen the hub genes related to GC from the Hypo-HGs,up-regulated hypomethylated oncogenes,Hyper-LGs and TSGs.GO and KEGG enrichment analysis were carried out on the hub genes.Results①We obtained 110 Hypo-HGs in the GC tissues,including FN1,COL3A1 and COL1A1,among which 9 genes such as TAC1,TWIST1,UCHL1,SPARC,GREM1,MEF2C and MAFB were hypomethylated oncogenes with up-regulated expression.There were 23 Hyper-LGs,such as CDH1,FOXA1 and KLF4,among which AZGP1 and CDH1 were TSGs.②The biological process of Hypo-HGs mainly in

关 键 词：胃癌 胃癌基因 胃癌发病核心基因 差异表达基因 基因甲基化 差异表达甲基化基因 

分 类 号：R181.3[医药卫生—流行病学]