应用生物信息学方法筛选与早期胃癌预后相关的核心基因  

Application of bioinformatics analysis to screen core genes related to prognosis of early gastric cancer

作　　者：邓建忠[1] 刘秀玲 陆文斌[1] 张华[1] 李文晶 吴颉[1] 刘迁 DENG Jianzhong;LIU Xiuling;LU Wenbin;ZHANG Hua;LI Wenjing;WU Jie;LIU Qian(Wujin Hospital Affiliated to Jiangsu University,Changzhou 213017,China)

机构地区：[1]江苏大学附属武进医院徐州医科大学武进临床学院,江苏常州213017

出　　处：《山东医药》2021年第10期1-5,共5页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81872275);江苏省卫健委高层次卫生人才“六个一工程”拔尖人才科研项目(LGY2018017);常州市卫生计生委青年人才科技项目(QN201729)。

摘　　要：目的应用生物信息学方法筛选与早期胃癌预后相关的核心基因。方法以“early gastric cancer,Homo”为关键词,从GEO数据库中下载人类早期胃癌基因芯片数据集(GSE3438、GSE55696)。利用GEO2R在线分析工具筛选早期胃癌组织与正常胃组织的差异表达基因(DEGs),采用维恩图确定GSE3438、GSE55696数据集的交集基因。利用生物学信息注释数据库DAVID对早期胃癌DEGs进行GO功能注释和KEGG富集分析。应用STRING在线数据库,以medium confidence>0.4为条件构建DEGs的蛋白质相互作用网络,并通过Cytoscape的CytoHubba插件按基因节点的连接度筛选前6位核心基因。以核心基因mRNA表达的最佳截断值为临界值,将早期胃癌患者分为高表达者与低表达者,比较不同表达者的总生存期(OS)。结果从GSE3438、GSE55696数据集中共获取30个DEGs,其中表达上调基因11个、表达下调基因19个。GO功能注释显示,早期胃癌的DEGs主要存在于细胞外外来体的细胞学组分,介导烟酰胺腺嘌呤二核苷酸(NAD)或烟酰胺腺嘌呤二核苷酸磷酸(NADP)为受体的氧化还原酶活性的生物学功能,参与细胞增殖调控的生物学过程。KEGG富集分析显示,DEGs主要参与糖酵解和糖异生以及细胞色素P450信号通路的调控。通过Cytoscape的CytoHubba插件按基因节点的连接度筛选前6位核心基因,分别为CDKN2A、ANXA2、CTSB、ATF3、CD59、CCND2。ANXA2高表达者中位OS高于ANXA2低表达者,CTSB高表达者中位OS低于CTSB低表达者(P均<0.01);CCND2、CD59、ATF3、CDKN2A不同表达者中位OS比较P均>0.05。结论早期胃癌组织存在多种DEGs,其中ANXA2、CTSB表达变化可能与早期胃癌患者预后有关。Objective To screen out the core genes related to the prognosis of early gastric cancer(EGC)by bioin⁃formatics analysis.Methods Human early gastric cancer gene chip datasets(GSE3438 and GSE55696)were downloaded from GEO database by taking"Early Gastric Cancer(HOMO)"as key words.GEO2R online analysis tool was used to screen out the differentially expressed genes(DEGs)between the early gastric cancer tissues and normal gastric tissues,and Venn diagram was utilized to identify the intersection genes of GSE3438 and GSE55696 datasets.GO functional anno⁃tation and KEGG enrichment analysis were performed on DEGs of early gastric cancer by using biological information anno⁃tation database DAVID.The online STRING database was used to construct the protein-protein interaction(PPI)network of DEGs with the condition of medium confidence>0.4,and the first six core genes were screened out by Cytohubba plugin of Cytoscape according to the connectivity degree of gene nodes.Taking the best cutoff value of core gene mRNA expres⁃sion as the critical value,the patients with early gastric cancer were divided into the high expression group and the low expression group,and the overall survival(OS)of the different expression groups was compared.Results A total of 30 DEGs were obtained from GSE3438 and GSE55696 datasets,of which 11 genes were up-regulated and 19 genes were downregulated.GO functional annotation showed that DEGs mainly existed in the extracellular foreign body cell components,mediated the biological function of oxidoreductase activity with aldehyde dehydrogenase(NAD)activity or NADP as the re⁃ceptor,and was involved in the cell proliferation-regulated biological processes.KEGG enrichment analysis showed that DEGs were mainly involved in the regulation of glycolysis/gluconeogenesis and cytochrome P450 signaling pathways.The first six core genes were screened out by Cytoscape Cytohubba plug-in according to the connectivity of gene nodes,which were CDKN2A,ANXA2,CTSB,ATF3,CD59,and CCND2.The median OS of the patients

关 键 词：早期胃癌 生物信息学方法 核心基因 预后 

分 类 号：R735.2[医药卫生—肿瘤]