Screening For Key Genes Of Hepatocellular Carcinoma And Analysing On Their Functions Based On Bioinformatics

Objective: The differentially expressed genes(DEGs)of hepatocellular carcinoma(HCC)were screened by using bioinformatics analysis,and their fuctions in the occurrence and development of HCC were explored to provide new ideas for the diagnosis,treatment and prevention of HCC.Methods:(1)The DEGs of HCC and normal liver tissues in datasets GSE102079,GSE121248,GSE84402 and GSE60502 were obtained using R language.The GO function analysis and KEGG pathway enrichment analysis of DEGs were carried out using DAVID database.(2)The protein-protein interaction(PPI)network was constructed by using STRING database,and the obtained files were imported into Cytoscape software for visual analysis of PPI network,and cytoHubba was used to screen key genes.(3)To verify the key genes,the GEPIA database was used to analyze the relationship between the key genes and the prognosis of HCC patients.Then the UALCAN,Oncomine databases and qRT-PCR assay were used to detect the mRNA expression levels of the key genes in HCC and normal tissues.Finally,the HPA database was used to show the differences in the protein level of key genes.(4)The LinkedOmics database was used to find the relationship between candidate genes and clinical features of HCC.(5)NetworkAnalyst online tool was used to obtain the transcription factors(TFs)and GEPIA was used to analyze theirs correlation with key genes.Results:(1)591 up-regulated genes significantly expressed in HCC have been screened,which are mainly involved in cell cycle,DNA replication,pyrimidine metabolism,p53 signaling pathway and others,and they are closely related to the pathogenesis of HCC.Venn showed that 51 genes are simultaneously enriched in the top 10 KEGG/GO.(2)The top 10 key genes screened from the PPI network constructed by 51 up-regulated genes are CDK1,CCNB2,CCNB1,CDC20,BUB1,MAD2L1,MCM3,BUB1 B,MCM2 and RFC4.(3)GEPIA database analysis showed that high expression of the nine other genes except CCNB2 is associated with poor survival in HCC patients.UALCAN,Oncomine and qRT-PCR analysis showed that these nine genes are significantly highly expressed in HCC tissues.HPA database results showed that the immunohistochemical staining of CDK1,CCNB1,CDC20,MAD2L1,MCM3,MCM2 and RFC4 are positive in HCC tissues.(4)The LinkedOmics database showed that the key genes are correlated with overall survival,overall stage,pathology T stage,race and the age of onset.(5)TF analysis showed that MYBL2,KDM5 B,MYC,SOX2 and E2F4 are TFs regulating the nine key genes.Correlation analysis showed that MYC is significantly positively correlated with the expression of CCNB1,BUB1,MAD2L1,MCM3 and BUB1 B,while the four other TFs are significantly positively correlated with the expression of these nine genes.Conclusions: CDK1,CCNB1,CDC20,BUB1,MAD2L1,MCM3,BUB1 B,MCM2and RFC4 are significantly highly expressed in HCC and can predict poor prognosis of HCC,which may be potential therapeutic targets for HCC.