DNA methylation and gene expression profiles show novel regulatory pathways in hepatocellular carcinoma

摘要: Alcohol is a well-known risk factor for hepatocellular carcinoma (HCC), but the mechanisms underlying alcohol-related hepatocarcinogenesis are still poorly understood. alters provision of methyl groups within hepatic one-carbon metabolism, possibly inducing aberrant DNA methylation. Whether specific pathways epigenetically regulated in alcohol-associated HCC is, however, unknown. The aim present study was to investigate genome-wide promoter methylation and gene expression profiles non-viral, HCC. From eight patients undergoing curative surgery, array-based data all annotated genes were analyzed by comparing tissue homologous cancer-free liver tissue. After merging with data, we identified 159 hypermethylated-repressed, 30 hypomethylated-induced, 49 hypermethylated-induced, 56 hypomethylated-repressed genes. Notably, emerged as novel regulatory mechanism transcriptional repression controlling retinol metabolism (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22, RDH16), iron homeostasis (HAMP), (SHMT1), putative, newly function tumor suppressors (FAM107A, IGFALS, MT1G, MT1H, RNF180). A approach merged allowed identifying number novel, candidate tumor-suppressor hepatocarcinogenesis. Retinol SHMT1 also through Due reversibility epigenetic environmental/nutritional factors, these findings may open up interventional strategies prevention related alcohol, modifiable dietary component.