Prognostic effect of DNA methylation of BTG2 gene in Chinese hepatocellular carcinoma.

BACKGROUND: This study aims to develop a prognostic model for overall survival based on potential methylation sites within B-cell translocation gene 2 ( BTG2 ) in Chinese patients with hepatocellular carcinoma (HCC).

METHODS: This is a retrospective study. The beta values of nine CpG sites and RSEM normalized count values of BTG2 gene were extracted from the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) (TCGA-LIHC) dataset, with the beta value representing the methylation level by indicating the ratio of the intensity of the methylated bead type to the combined locus intensity. Pyrosequencing was performed to determine the range of methylation values surrounding cg01798157 site in BTG2 gene. A weighted linear model was developed to predict the overall survival (OS).

RESULTS: The beta value of cg01798157 was significantly negatively associated with the mRNA expression of BTG2 in the TCGA-LIHC dataset (Spearman's rho = -0.5306, P  = 2.27 × 10-27 ). The methylation level of cg01798157 was significantly associated with OS in the cohort of 51 Chinese HCC patients (Hazard ratio = 0.597, 95% CI: 0.434-0.820, P  = 0.001). Multivariate Cox regression analysis identified methylation level of cg01798157, cirrhosis, and microvascular invasion as independent prognostic factors. The prognostic efficiency of death risk score was superior to that of cirrhosis or microvascular invasion alone.

CONCLUSIONS: The methylation level of cg01798157 in BTG2 may be an epigenetic biomarker in Chinese patients with resectable HCC.