基于生物信息学方法筛选乙型肝炎病毒相关肝癌的关键基因和临床预后  

Identification of potential key genes and clinical prognosis in hepatitis B virus-associated hepatocellular carcinoma by bioinformatics

作　　者：李玉杰 杨雪佳 吴登强 吕玥茜 李茵佳 周素芳[1] LI Yu-jie;YANG Xue-jia;WU Deng-qiang;LV Yue-xi;LI Yin-jia;ZHOU Su-fang(School of Basic Medicine,Guangxi Medical University,Nanning 530021,Guangxi,CHINA)

机构地区：[1]广西医科大学基础医学院,广西南宁530021

出　　处：《海南医学》2020年第24期3129-3134,共6页Hainan Medical Journal

基　　金：国家自然科学基金(编号:81872491)。

摘　　要：目的基于基因芯片和生物信息学相关的分析方法,筛选与慢性乙型肝炎(HBV)相关肝细胞癌(HCC)发病的差异表达基因,为有HBV感染史的肝癌患者提供新的分子治疗靶点。方法本研究对来自基因表达数据库(GEO)的GSE55092和GSE121248的mRNA微阵列数据进行分析,获得HBV相关性肝癌和正常组织的差异表达基因(DEGs),利用DAVID数据库对DEGs进行了GO功能分析和KEGG通路富集分析,利用String数据库构建了蛋白质-蛋白质相互作用(PPI)网络,hub基因使用Cytoscape软件进行筛选,cBioportal分析hub基因的相关性,使用GEPIA和Kaplan-Meier数据库并结合TCGA数据库中肝癌基因表达数据进行验证,探讨hub基因与肝癌发生、发展和预后的关系。结果共获得了129个DEGs,鉴定了三个hub基因,细胞周期素依赖性激酶1(CDK1)、细胞周期蛋白B1(CCNB1)和DNA拓扑异构酶(TOP2A)与细胞周期、嘧啶代谢和DNA复制有关,并且三个基因高度相关,GEPIA数据库证实这些基因在肝癌组织中高度表达,并获得了相关的预后信息,Kaplan-Meier显示其与HCC患者的低生存率相关。结论CDK1、CCNB1和TOP2A与肝癌分级高度相关,肝细胞癌中hub基因的mRNA表达明显高于癌旁组织,hub基因为HBV相关肝癌的研究提供了新方向,有可能成为新的治疗靶点。Objective Based on microarray and bioinformatics analysis,to screen differentially expressed genes in the pathogenesis of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC),in order to provide a new molecular therapeutic target for HCC patients with HBV infection history.Methods The mRNA microarray data of GSE55092 and GSE121248 from gene expression database(GEO)were analyzed to obtain the differentially expressed genes(DEGs)in HBV-related hepatocellular carcinoma and normal tissues.GO function analysis and KEGG pathway enrichment analysis of DEGs were carried out using David database.Protein-protein interaction(PPI)network was constructed by using string database.Cytosacp software was used to screen hub gene,and cBioportal was used to analyze the correlation of hub gene.Gepia and Kaplan-Meier databases and TCGA database were used to verify the relationship between hub gene and the occurrence,development and prognosis of HCC.Results A total of 129 DEGs were obtained and three hub genes,cyclin-dependent kinase 1(CDK1),cyclin B1(CCNB1),and DNA topoisomerase(TOP2A)were identified to be related to cell cycle,pyrimidine metabolism,and DNA replication.The three hub genes were highly correlated.The GEPIA database confirmed that these genes were highly expressed in HCC tissues,and relevant prognostic information was obtained.Kaplan-Meier showed that they were associated with low survival in HCC patients.Conclusion CDK1,CCNB1,and TOP2A are highly correlated with the grading of liver cancer.The mRNA expression of hub gene in hepatocellular carcinoma is significantly increased compared with that in adjacent tissues.The hub gene provides a new direction for the study of HBV-related liver cancer and may become a new therapeutic target.

关 键 词：肝细胞癌 慢性乙肝病毒 基因芯片 差异表达基因 细胞周期素依赖性激酶1 细胞周期蛋白B1 拓扑异构酶 

分 类 号：R735.7[医药卫生—肿瘤]