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

Anticancer Res. 2007 Jul-Aug;27(4B):2269-74.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Cadherins / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • DNA Methylation
  • Female
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymerase Chain Reaction / methods
  • Prognosis
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • Cadherins
  • RNA, Messenger
  • M-cadherin