Identification of specific DNA methylation sites on the Y-chromosome as biomarker in prostate cancer

Oncotarget. 2015 Dec 1;6(38):40611-21. doi: 10.18632/oncotarget.6141.

Abstract

As a diagnostic biomarker, prostate special antigen (PSA) tests always generate false positive results and lead to unnecessary and/or repeat biopsies. Therefore, there is an urgent need for developing more sensitive, specific diagnostic biomarkers. We epigenotyped methylated sites in cancer tissues and adjacent normal tissues from 66 patients. In comparison with normal adjacent tissues, we observed that there were 6 aberrant methylation sites in prostate cancer tissues on the Y-chromosome. We further performed pyrosequencing using urine of PCa patients and we identified one methylated site (cg05163709) as a potential biomarker. We evaluated the predictive capacity of the aberrant methylated sites using the area under receiver operating characteristic (ROC) curve (AUC). The ROC analysis showed a higher AUC for cg05163709 (0.915) than prostate-specific antigen (PSA, 0.769). These results indicated that aberrant DNA methylation of cg05163709 on the Y-chromosome could serve as a potential diagnostic biomarker with high sensitivity and specificity.

Keywords: DNA methylation; Y-chromosome; biomarker; prostate cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Chromatin Immunoprecipitation
  • Chromosomes, Human, Y / genetics*
  • DNA Methylation*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics*
  • ROC Curve
  • Real-Time Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • Prostate-Specific Antigen