摘要
目的通过生物信息学方法筛选出肝癌中的关键基因,并预测其在肝癌发生中的潜在分子机制及其对肝癌预后的影响。方法通过基因表达综合数据库(GEO)下载3个肝癌微阵列数据集,进行差异分析并取其交集。利用DAVID数据库对187个差异表达基因(DEGs)进行功能富集分析。通过STRING数据库及Cytoscape软件构建DEGs的蛋白-蛋白相互作用(PPI)网络及筛选关键基因。利用GEPIA、GSCALite数据库进行关键基因通路、表达验证及预后分析。结果获得185个3个数据集交集的DEGs,包括54个上调基因和131个下调基因,这些基因生物功能主要富集在细胞分裂和细胞凋亡,主要参与细胞周期、DNA复制、Rap1信号通路的调节。在PPI网络中筛选出10个关键基因,分别为胸苷激酶1(TK1)、细胞分裂周期相关5(CDCA5)、甲状腺激素受体相互作用体13(TRIP13)、着丝粒蛋白M(CENPM)、异常纺锤形微管组件(ASPM)、着丝粒蛋白F(CENPF)、微型染色体维护复合体组件49(MCM4)、霍利迪连接体识别蛋白(HJURP)、母体胚胎亮氨酸拉链激酶(MELK)、非染色体结构维护凝缩蛋白Ⅰ复合体G亚基(NCAPG)。关键基因在肝癌中高表达,除UBE2C外,关键基因高表达与肝癌患者总生存率低相关。结论关键基因与肝癌的发生和预后不良有关。
Objective To screen out the key genes in hepatocellular carcinoma(HCC)and predict the influence of key genes on the occurence and prognosis of HCC by bioinformatics analysis.Methods Three microarray datasets were downloaded from the Gene Expression Omnibus database(GEO)to obtain overlapping differentially expressed genes(DEGs).Then,the function enrichment analyses of 187 DEGs were finished by DAVID database.Protein-protein interaction(PPI)network was constructed by STRING and Cytohubba was used to screen the key genes.The signaling pathway,expression and prognosis of key genes were analyzed using GEPIA and GSCALite.Results 185 DEGs were obtained,comprising 54 upregulated and 131 downregulated genes.The biological processes of DEGs were mainly enriched in cell division and apoptotic process.They were mainly involved in Cell cycle,DNA replication,Rap1 signaling pathway.Ten key genes[thymidine kinase 1(TK1),cell cycle related 5(CDCA5),thyroid hormone receptor interacting body 13(TRIP13),centromere m(CENPM),abnormal spindle microtubule assembly(ASPM),centromerin F(CENPF),micro chromosome maintenance complex module 49(MCM4),Holliday junction recognition protein(HJURP),maternal embryo leucine zipper kinase(MELK),non chromosome structure maintenance coagulation G subunit of contractile protein I complex(NCAPG)]were screened out,and verified to be highly expressed in HCC and predicted poor prognosis.Conclusion The key genes are associated with the occurrence and poor prognosis of HCC.
作者
石丽稳
王华桥
杨铁成
杨丽洁
王丹雯
李炫飞
冯茂辉
陈志芬
Shi Liwen;Wang Huaqiao;Yang Tiecheng;Yang Lijie;Wang Danwen;Li Xuanfei;Feng Maohui;Chen Zhifen(Department of Gastroenterology,Zhongnan Hospital of Wuhan University,Hubei Clinical Center and Key Laboratory for Intestinal and Colorectal Diseases,Wuhan 430071,China;Department of Gastrointestinal Surgery,Zhongnan Hospital of Wuhan University,Clinical Medical Research Center of Peritoneal Cancer of Wuhan,Clinical Cancer Study Center of Hubei Provence,Key Laboratory of Tumor Biological Behavior of Hubei Provence,Wuhan 430071,China)
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2020年第9期1724-1727,共4页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金(81770283)
武汉市腹膜癌临床医学研究中心资助项目(2015060911020462)
武汉大学中南医院创新培育基金(znpy2018004)。
关键词
肝癌
关键基因
生物信息学分析
预后
Hepatocellular carcinoma
Key genes
Bioinformatics analysis
Prognosis
