title: Serum GADD45a methylation is a useful biomarker to distinguish benign vs malignant prostate disease.
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.
authors.affiliation: 1] Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA [2] Division of Biostatistics, Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: I M
authors.initials: IM
authors.lastname: Reis
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ramachandran
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: C
authors.initials: C
authors.lastname: Speer
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gordian
authors.affiliation: 1] Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA [2] Division of Hematology/Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA [3] Miami VA Medical Center, Miami, FL, USA.
authors.forename: R
authors.initials: R
authors.lastname: Singal
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D018797:Cell Cycle Proteins / Q000097:blood* / Q000235:genetics; D004247:DNA / Q000097:blood; D019175:DNA Methylation; D003937:Diagnosis, Differential; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000097:blood* / Q000235:genetics; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D012680:Sensitivity and Specificity; D000097642:GADD45 Proteins
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004247:DNA; D009687:Nuclear Proteins; D017430:Prostate-Specific Antigen; C439070:GADD45A protein, human; D000097642:GADD45 Proteins