HCC关键基因的筛选及其对患者生存预后的临床意义

Screening of key genes of HCC and its clinical significance for survival and prognosis of patients

目的分析肝细胞癌(Hepatocellular carcinoma,HCC)的关键基因,为HCC临床早期诊断、治疗和判断总体生存预后提供依据。方法从GEO数据库下载HCC相关的GSE121248芯片数据,利用GEO2R在线分析工具筛选差异表达基因(Differential Expression Genes,DEGs),并对筛选的DEGs进行GO(Gene Ontology,GO)功能注释和KEGG(Kyoto Encyclopedia of Gene and Genome,KEGG)通路富集分析;利用String数据库和Cytoscape软件Hubba插件的MCC算法对DEGs进行PPI(Protein-protein interaction,PPI)网络绘制和Hub基因筛选;利用Kaplan-Meier Plotter、GEPIA和cBioPortal等数据库对关键基因进行总体生存、基因表达量、基因突变和共表达关系分析。结果分析后共得到186个DEGs,其中表达上调38个,表达下调148个;其GO功能主要富集在小分子分解代谢过程、核苷酸代谢过程、糖胺聚糖结合、有丝分裂细胞周期G2/M转换的正调节等;而KEGG主要富集在P53信号通路、癌症中的蛋白多糖等通路上;通过对DEGs进行PPI网络绘制,筛选出10个排名并列第一的Hub基因,包括DTL、HMMR、TOP2A、CCNB1、CDK1、ECT2、BUB1B、NEK2、CDKN3和RACGAP1。Hub基因在HCC癌组织中存在共表达关系,且均高表达,同时也发生一定的突变,其突变显著缩短HCC患者的无病生存时间。结论通过生物信息学分析筛选出HCC预后的Hub基因,为其治疗和药物靶点的选择提供依据。

Objective To analyze the key gene(Hub gene)of hepatocellular carcinoma(HCC),so as to provide evidence for early clinical diagnosis,treatment and overall survival and prognosis of HCC.Methods HCC GSE121248 chip data from GEO database were downloaded,differentially expressed genes(DEGs)were screened with GEO2R online analysis tool,and GO function annotation and KEGG pathway enrichment were analyzed on the screened DEGs.PPI network drawing and Hub gene screening of DEGs were carried out by using String database and MCC algorithm of Hubba plug-in of Cytoscape software.Then,Kaplan-Meier Plotter,GEPIA and cBioPortal databases were used to analyze the overall survival,gene expression,gene mutation and co-expression of key genes.Results We got 186 DEGs from HCC data,of which 38 were up-regulated and 148 were down-regulated.It mainly concentrated its GO function in small molecule catabolism,nucleotide metabolism,glycosaminoglycan binding,positive regulation of G2/M transition in mitotic cell cycle,etc.,while KEGG was mainly concentrated in P53 signaling pathway and proteoglycan pathway in cancer,etc.Ten Hub genes,including DTL,HMMR,TOP2A,CCNB1,CDK1,ECT2,BUB1B,NEK2,CDKN3 and RACGAP1,were screened out by plotting PPI network of DEGs.Hub gene was co-expressed in HCC tissues,and all of them are highly expressed.HUB gene also had some mutations,which significantly shortens the disease-free survival time of HCC patients.Conclusion Through bioinformatics analysis,Hub gene of HCC prognosis was screened out,which provided the basis for its treatment and drug target selection.