Identification of potential key genes and pathways in hepatitis B virus-associated hepatocellular carcinoma by bioinformatics analyses

Chronic hepatitis B virus (HBV) is one of the leading causes of hepatocellular carcinoma (HCC). The precise molecular mechanisms by which HBV contributes to HCC development are not fully understood. The key genes and pathways involved in the transformation of nontumor hepatic tissues into HCC tissues in patients with HBV infection are essential to guide the treatment of HBV-associated HCC. Five datasets were collected from the Gene Expression Omnibus database to form a large cohort. Differentially expressed genes (DEGs) were identified between HCC tissues and nontumor hepatic tissues from HBV-infected patients using the ‘limma’ package. The top 50 upregulated and top 50 downregulated DEGs in HCC vs. nontumor tissues were demonstrated in subsets by heat maps. Based on the DEGs, Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathways enrichment analyses were performed. Several key pathways of the up- and downregulated DEGs were identified and presented by protein-protein interaction (PPI) networks. A total of 1,934 DEGs were identified. The upregulated DEGs were primarily associated with the ‘cell cycle’. Among the DEGs enriched in the ‘cell cycle’ pathway, 6 genes had a log(2)-fold change >2: SFN, BUB1B, TTK, CCNB1, CDK1 and CDC20. The downregulated DEGs were primarily associated with the metabolic pathways, such as ‘carbon metabolism’, ‘glycine, serine and threonine metabolism’, ‘tryptophan metabolism’, ‘retinol metabolism’ and ‘alanine, aspartate and glutamate metabolism’. The DEGs in the ‘cell cycle’ and ‘metabolic pathways’ were presented by the PPI networks respectively. Overall, the present study provides new insights into the specific etiology of HCC and molecular mechanisms for the transformation of nontumor hepatic tissues into HCC tissues in patients with a history of HBV infection and several potential therapeutic targets for targeted therapy in these patients.