CpG Island Methylator Phenotype Association With Metastasis And Prognostic In Hepatocellular Carcinoma

Purpose:The promoter methylation of gene is an important epigenetic modification, which can bind methyl-CpG-binding domain and histone acetylation cause gene expression silence.CpG island methylator phenotype(CIMP),in which multiple genes are concurrently methylated has been recognized as one of the important mechanisms in hepatocellular carcinoma and associated with elevated serum alpha-fetoprotein level.We wanted to investigate the promoter methylation of gene,confirm CIMP associated prognostic in HCC and analyze relationship between CIMP status and clinicopathologic features.Experimental Design:we examined the promoter methylation status of ten genes P15, SYK,TIMP-3,E-cadherin,RASSAF1,P53,RB1,WT1,P14 and P16 in 60 HCC and 60 paired non-tumor tissues by methylation-specific PCR.Hepatocellular carcinoma was detected by an evaluation of CIMP.We compared the clinicopathologic features of hepatocellular carcinoma that had CIMP-High with tumors that had CIMP-Intermediate and CIMP-Negative.Results:The frequency of promoter methylation of ten genes in 60 HCC varied from 8%in P53 to 90%in p14.The average methylated-gene numbers were significantly different between HCC and paired non-tumor tissues(P＜0.05),we found metastasis;GGT and TNM were significantly different among patients with different CIMP status through multiple statistical analysis.Patients who had CIMP-H hepatocellular tumors had a significantly worse survival than patients who had CIMP-I tumors(P＜0.01) or CIMP-N tumors(P＜0.05).But there is not different between CIMP-I tumors and CIMP-N tumors.Conclusion:Positive correlation of CIMP and metastasis in HCC suggests that CIMP can serve as a molecular marker of late stage of HCC development and can cause poor prognosis...