To test this hypothesis, the clinical relevance of promoter methylation of TGFBR2, SMAD4, SMAD7 and SNAI1 genes in HCC was evaluated by correlating the percentage of methylation/non-methylation with clinical and biological parameters, including overall survival, tumor grade, recurrence, metastasis and serum alpha-fetoprotein levels. The gene discussed is SMAD4; the disease is hepatocellular carcinoma.