To screen prognostic biomarkers and potential therapeutic drugs in hepatocellular carcinoma based on weighted gene co-expression network analysis
Objective To screen biomarkers associated with adverse prognosis in hepatocellular carcinoma(HCC),exploring the possible pathogenesis of HCC at the molecular level,and to predict drug candidates with potential thera-peutic effects in HCC.Methods The transcriptomic data of HCC and its clinical records were downloaded from the TCGA database and the GEO database.The gene expression profiles were analyzed by weighted gene co-expression net-work analysis(WGCNA)and differential expression gene analysis respectively.The intersection of the most positively correlated modular genes and the differentially expressed genes in the two datasets were selected as the key genes.Func-tional enrichment analysis of key genes was performed using GO and KEGG.PPI networks were constructed using the STRING database,and hub genes were identified by correlation analysis of key genes using Cytoscape software.Survival survival analysis was performed using the R language package K-M to clarify the relationship between core genes and the prognosis of HCC patients.Screening of potential therapeutic drugs for HCC was performed jointly using the online data-bases DGIdb and DREMIT.The prediction results were ranked based on the number of drug target matches,preference score,and specificity score.The top-ranked drugs were selected as possible therapeutic drug candidates.Results A to-tal of 64 key genes were obtained,mainly enriched in cell cycle and division,DNA replication and damage repair,virus infection,P53 signaling pathway,etc.CDC20,KIF2C,CCNB2,KIF20A,CCNA2,TOP2A,UBE2C,NUSAP1,AURKA and TRX2 were identified as hub genes by PPI analysis.K-M survival analysis showed that CDC20,KIF20A,CCNA2 and TOP2A were significantly associated with the prognosis of HCC.Drug candidates with potential efficacy in HCC were jointly screened by DGIdb and DREMI,with Sorafenib,Dovitinib,Fluorouracil and Mitoxantrone ranking high in both DGIdb and DREMI.Conclusion CDC20,KIF20A,CCNA2 and TOP2A may be potential biomarkers of HCC prognosis,but further clinical studies are needed to validate them.The development of HCC may be related to vi-rus infection,cell cycle and division,DNA replication and damage repair,and the P53 signaling pathway.Sorafenib,Dovitinib,Fluorouracil and Mitoxantrone as potential clinical candidates for the treatment of HCC.
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