Validation of signature molecular profiles of advanced HCV liver disease in hepatocellular carcinoma patients.

Our previous transcriptome analysis revealed that hepatitis C virus (HCV) infection in hepatocytes regulates the expression of numerous hepatocellular genes in a liver disease stage-specific manner. Based on the fold changes at different stages and the known relevant function of the cellular genes with respect to hepatocellular carcinoma (HCC) and through comprehensive examination with various in silico assays, such as heatmap and volcano analysis for the differential expression, the Cancer Genome Atlas - Hepatocellular Carcinoma (TCGA-HCC) analysis, and molecular approaches, such as qRT-PCR, immunoblot analyses, we have chosen the two up-regulated genes - aldo-keto reductase family 1 member B10 (AKR1B10) and hexokinase domain containing 1 (HKDC1), and two down-regulated genes - glycine N-methyltransferase (GNMT) and C-type lectin domain family 4, member M (CLEC4M), and validated their differential expressions of the genes at disparate stages of liver disease with respect to the development of potential therapeutic targets against HCV-mediated hepatocellular carcinoma (HCC). These data suggested that the differentially expressed genes at various stages could serve as prognostic and diagnostic markers for liver disease progression and may also be utilized in developing therapeutic drugs.