Nine hub genes related to the prognosis of HBV-positive hepatocellular carcinoma identified by protein interaction analysis.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) represents the second highest cause of cancer-associated deaths worldwide, and hepatitis B virus (HBV) infection is a major risk factor. Here, we aimed to identify genetic signatures of HBV-positive (HBV+) HCC and uncover potential carcinogenic mechanisms. METHODS: Gene expression profiles of 124 HBV-positive samples, including tumor and non-tumor tissues were subjected to bioinformatics analysis. The expression levels of thymidylate synthase (TYMS) and CDC45 in patients' samples were validated by immunohistochemistry (IHC) and their association with patient survival was assessed by the Kaplan-Meier method. RESULTS: A total of 666 differentially expressed genes (DEGs) were identified. The 137 upregulated genes were mainly enriched in the cell cycle, P53 signaling pathway, and extracellular matrix-receptor interaction, whereas the 529 downregulated genes were enriched in cytochrome P450 xenobiotic and drug metabolism, and cytokine-cytokine receptor interaction. A total of 15 hub genes were identified from the protein-protein interaction (PPI) network and 10 of them were strongly associated with HBV+ HCC. The expression of 9 hub genes (CDK1, NDC80, TYMS, AURKA, FOXM1, CDC45, ZWINT, PBK, and TPX2) was associated with poor overall survival. Validation of TYMS and CDC45 protein expression levels in clinical samples by IHC showed that they were higher in HBV+ HCC than in HBV- HCC or normal tissue and were associated with poor patient survival. CONCLUSIONS: HBV may induce HCC through regulation of host gene expression. Among the hub DEGs identified, 9 key genes could be used as new prognostic biomarkers and treatment targets for HBV+ HCC.