Correlation of CpG island methylator phenotype with poor prognosis in hepatocellular carcinoma

CpG island methylator phenotype (CIMP), in which multiple genes are concurrently methylated, is an important mechanism in hepatocellular carcinoma development. We determined a hypermethylation profile in hepatocellular carcinoma (HCC). We examined the promoter methylation status of 10 genes in 60 cases of hepatocellular carcinoma (HCC), 60 cases of paired non-tumor tissues, and 6 cases of normal tissues by methylation-specific PCR. The average methylated gene numbers were significantly different between HCC and nontumor tissues (p<0.001). We found metastasis, gamma-glutamyl transpeptidase (GGT) and tumor node metastasis (TNM) stage were significantly different among patients with different CIMP status. Patients with high frequency CIMP tumors had significantly worse survival than patients with intermediate frequency or no CIMP tumors (p<0.01 and p<0.05, respectively). Our results suggested that CIMP could serve as a molecular marker of late stage and poorly prognostic HCC development. (C) 2009 Elsevier Inc. All rights reserved.