Frequent promoter methylation of M-cadherin in hepatocellular carcinoma is associated with poor prognosis

Background: Many cadherins (CDH) are associated with various types of cancer and their genetic and epigenetic alterations might be involved in carcinogenesis. Materials and Methods: We examined the methylation status of CDH genes in primary hepatocellular carcinoma (HCC) and corresponding noncancerous liver tissues derived from 47 patients, and evaluated the correlation with clinicopathological parameters. Results: Hypermethylation was detected at a ratio ranging from 0% to 55.3%. In particular, M-cadherin (CDH15) was the most hypermethylated of 7 CDH genes. Patients with methylated M-cadherin had shorter 5-year survival rates than patients with unmethylated M-cadherin (overall survival rates, 67.4% vs. 82.7%; p=0.0167) when assessed using Kaplan-Meier curves. Multivariate analysis revealed that M-cadherin methylation status was an independent predictor of survival. Conclusion: We found that M-cadherin methylation status has prognostic significance for the poorer survival of patients with HCC. This is the first definitive report of a correlation between M-cadherin and the prognosis of patients with HCC.