High-throughput sequencing-based analysis of gene expression of hepatitis B virus infection-associated human hepatocellular carcinoma.

Hepatitis B virus (HBV) infection is a critical factor for the initiation and progression of hepatocellular carcinoma (HCC). Gene expression profiles for HBV-associated HCC may provide valuable insight for the diagnosis and treatment of this type of HCC. The present study aimed to screen the differential genes in human HCC tissues based on high-throughput sequencing and to predict the potential therapeutic targets. Total mRNA was extracted from human HCC tissues and paracancerous tissues and sequenced using the Hiseq4000 sequencing platform. Differential gene expressions were screened and further analyzed using quantitative PCR and immunohistochemistry. A total of 2,386 differentially expressed genes were screened. Of these, 1119 were upregulated and 1,267 were downregulated in paracancerous tissues compared with tumor tissues. Gene Ontology term analysis demonstrated that differentially expressed genes were involved in carboxylic acid catabolism, monocarboxylic acid metabolic processes and α-amino acid metabolic processes. Molecular functional analysis revealed that the differentially expressed genes functioned in oxidoreductase activity, for example acting on CH-OH group of donors and permitting identical protein binding, anion binding, coenzyme binding and monocarxylic acid transporter activity. The Kyoto Encyclopedia of Genes and Genomes analysis reported that the differentially expressed genes were primarily concentrated in 20 signaling pathways, such as valine, leucine and leucine degradation, retinol metabolism and the cell cycle. Differential expression of proteins regulating the cell cycle, including stratifin, cyclin B1 and cyclin-dependent kinase 1, were significantly higher in tumor tissue compared with those in paracancerous tissue at both the mRNA and protein levels. These results were consistent with those obtained from high-throughput sequencing, indicating the reliability of the high-throughput sequencing. Together, these results identified differentially expressed genes and predicted the subsequent signaling pathways, which may be involved in the occurrence and development of HCC. Therefore, the present study may provide novel implications in the therapeutic and diagnosis of HCC.