Abstract
Background:Hepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus infection. We aimed to identify some core genes and pathways for HBV-related HCC. Methods: Gene expression profiles of GSE62232, GSE121248, and GSE94660 were available from Gene Expression Omnibus. The GEO2R online tool and Venn diagram software were applied to analyze commonly differentially expressed genes. Then functional enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Gene and Genome (KEGG) as well as the protein-protein interaction (PPI) network was conducted. The overall survival rates and the expression levels were detected by Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). Next, gene set enrichment analysis (GSEA) was performed to verify the KEGG pathway analysis. Furthermore, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to validate the levels of gene expression in tumor tissues from HBV related HCC patients, HBV-related liver cell lines, and transfection si-p53 and knock-out p53 liver cancer cell lines. Finally, the prediction of the ceRNA network was constructed with R software. Results: Fifteen highly expressed genes associated with significantly worse prognoses were selected and CCNB1, CDK1, and RRM2 in the p53 signaling pathway were identified as core genes. GSEA results showed highly-expressed samples of three core genes were all enriched in the p53 signaling pathway in a validation dataset(P<0.0001). Expression of these three core genes were consistently higher in tumor tissue samples (P<0.0001) and liver cancer cell lines (P<0.05). However, transfection si-p53 and knock-out p53 liver cancer cell lines had lower expression (P<0.05). LncRNAs, including NEAT1, MALAT1, XIST, AC021078.1, and SNHG16, were identified by close interactions with core genes. Conclusions: CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway and could be potential biomarkers and therapeutic targets for HBV-related HCC.