4.7 Article

Clinical Relevance of CDH1 and CDH13 DNA-Methylation in Serum of Cervical Cancer Patients

Journal

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 13, Issue 7, Pages 8353-8363

Publisher

MDPI
DOI: 10.3390/ijms13078353

Keywords

cancer biomarker; epigenomics; DNA-methylation; prognosis; translational cancer research

Funding

  1. COMET Center ONCOTYROL
  2. Austrian Federal Ministry BMVIT/BMWFJ (via FFG)
  3. Austrian Federal Ministry Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT)
  4. Special research Program Cell Proliferation, Cell Death in Tumors (Austrian Science Fund) [SFB021]

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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.

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