Increasing interest has been given to the epigenetic regulation by DNA methylation in cancer development including hepatocellular carcinoma (HCC). Alcohol is a major risk factor for HCC although the mechanisms underlying the alcohol-related liver carcinogenesis are still incompletely understood. Alcohol is linked both to carcinogenesis and to aberrant DNA methylation by interfering with methyl group transfer within one-carbon metabolism through reactions mainly occurring in the liver. The effort to identify epigenetically-regulated pathways in alcohol-related HCC is therefore of great interest. Aim of the present study was to investigate the genome-wide promoter DNA methylation patterns together with array-based, gene expression profiles of non-viral, alcohol-related HCC. The methylation and gene expression profiles of all annotated genes were assessed in HCC tissue compared to tumor-free tissue, using a genome-wide, array-based approach in liver samples of eight patients undergoing curative surgery. The merging of DNA methylation and gene expression data allowed the detection of 160 hypermethylated-repressed, 31 hypomethylated -induced, 50 hypermethylated-induced and 56 hypomethylated-repressed genes. The analysis of transcriptionally-repressed genes associated with promoter hypermethylation enabled to identify several candidate tumor-suppressor genes, among which also a number of gene belonging to retinol metabolism (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22 and RDH16), and SHMT1 a key gene of one-carbon metabolism. DNA methylation at promoter site appears to regulate the expression of genes involved in retinol and one-carbon metabolism in alcohol-related HCC.
File in questo prodotto:
Non ci sono file associati a questo prodotto.