Clinical relevance of CDH1 and CDH13 DNA-methylation in serum of cervical cancer patients

Int J Mol Sci. 2012;13(7):8353-63. doi: 10.3390/ijms13078353. Epub 2012 Jul 5.

Abstract

This study was designed to investigate the DNA-methylation status of E-cadherin (CDH1) and H-cadherin (CDH13) in serum samples of cervical cancer patients and control patients with no malignant diseases and to evaluate the clinical utility of these markers. DNA-methylation status of CDH1 and CDH13 was analyzed by means of MethyLight-technology in serum samples from 49 cervical cancer patients and 40 patients with diseases other than cancer. To compare this methylation analysis with another technique, we analyzed the samples with a denaturing high performance liquid chromatography (DHPLC) PCR-method. The specificity and sensitivity of CDH1 DNA-methylation measured by MethyLight was 75% and 55%, and for CDH13 DNA-methylation 95% and 10%. We identified a specificity of 92.5% and a sensitivity of only 27% for the CDH1 DHPLC-PCR analysis. Multivariate analysis showed that serum CDH1 methylation-positive patients had a 7.8-fold risk for death (95% CI: 2.2-27.7; p = 0.001) and a 92.8-fold risk for relapse (95% CI: 3.9-2207.1; p = 0.005). We concluded that the serological detection of CDH1 and CDH13 DNA-hypermethylation is not an ideal diagnostic tool due to low diagnostic specificity and sensitivity. However, it was validated that CDH1 methylation analysis in serum samples may be of potential use as a prognostic marker for cervical cancer patients.

Keywords: DNA-methylation; cancer biomarker; epigenomics; prognosis; translational cancer research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Cadherins / blood
  • Cadherins / genetics*
  • DNA Methylation
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / genetics
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / blood*
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Promoter Regions, Genetic
  • Uterine Cervical Neoplasms / blood*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / mortality

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • DNA, Neoplasm
  • H-cadherin