Serum GADD45a methylation is a useful biomarker to distinguish benign vs malignant prostate disease

Br J Cancer. 2015 Jul 28;113(3):460-8. doi: 10.1038/bjc.2015.240. Epub 2015 Jul 14.

Abstract

Background: Prostate-specific antigen (PSA) screening for prostate cancer results in a large number of unnecessary prostate biopsies. There is a need for specific molecular markers that can be used in combination with PSA to improve the specificity of PSA screening. We examined GADD45a methylation in blood DNA as a molecular marker for prostate cancer diagnosis.

Methods: The study included 82 men, with PSA levels >4 ng ml(-1) and/or abnormal digital rectal exam, who underwent prostate biopsy. We compared GADD45a methylation in DNA from serum and buffy coat in 44 patients (22 prostate cancer and 22 benign). GADD45a methylation in serum DNA was examined in 82 patients (34 cancer and 48 benign).

Results: There was no significant difference in buffy coat GADD45a methylation between cancer and benign patients. Serum GADD45a methylation was significantly higher in cancer than in benign patients. Classification and regression tree predictive model for prostate cancer including risk groups defined by PSA, free circulating DNA (fcDNA) level and GADD45a methylation yielded specificity of 87.5%, sensitivity of 94.1% and receiver operator characteristic curve area of 0.937.

Conclusions: Serum GADD45a methylation in combination with PSA and fcDNA level was useful in distinguishing benign from prostate cancer patients.

MeSH terms

  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / genetics
  • Cell Cycle Proteins / blood*
  • Cell Cycle Proteins / genetics
  • DNA / blood
  • DNA Methylation*
  • Diagnosis, Differential
  • Humans
  • Male
  • Nuclear Proteins / blood*
  • Nuclear Proteins / genetics
  • Predictive Value of Tests
  • Prostate-Specific Antigen / blood
  • Prostatic Hyperplasia / blood
  • Prostatic Hyperplasia / diagnosis*
  • Prostatic Hyperplasia / genetics
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • GADD45A protein, human
  • Nuclear Proteins
  • DNA
  • Prostate-Specific Antigen