Comprehensive characterization of cancer genes in hepatocellular carcinoma genomes

Abstract

The present study was performed to detect moderate or low-frequency mutated cancer driver genes in hepatocellular carcinoma (HCC), using OncodriveFM and Dendrix. Following this, integrated analyses were conducted on these novel cancer driver genes. A total of 112,980 somatic mutations were retrieved from TCGA and classified into 11 categories based on their function. Driver genes and pathways were predicted by OncodriveFM and Dendrix, followed by differential expression, DNA-methylation, copy number variations and survival analyses. Overall, non-synonymous mutations accounted for >60% (72,149/112, 980) of total variants, 108 and 3 driver genes were determined by OncodriveFM and Dendrix, respectively. Tumor protein p53, SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4, smad family member 3, RB transcriptional corepressor 1, catenin β 1, smad family member 4, mitogen-activated protein kinase 1 and TSC complex subunit 2 are at the core of the driver gene interaction network. Two genes, transportin 1 (TNPO1) and chaperonin containing TCP1 subunit 3 (CCT3), were hypomethylated and overexpressed, and high expression of TNPO1 and CCT3 indicated a poor prognosis in patients with HCC. β-carotene oxygenase 2 was hypermethylated, under-expressed and associated with favorable prognosis in HCC. The present study has identified a set of novel cancer genes and pathways, offering potential therapeutic targets and prognostic biomarkers for the treatment of HCC.