title: DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy.
abstract: BACKGROUND
  We analysed critically the potential usefulness of RNA- and DNA-based biomarkers in supporting conventional histological diagnostic tests for prostate carcinoma (PCa) detection.
  
  
  METHODS
  Microarray profiling of gene expression and DNA methylation was performed on 16 benign prostatic hyperplasia (BPH) and 32 cancerous and non-cancerous prostate samples extracted by radical prostatectomy. The predictive value of the selected biomarkers was validated by qPCR-based methods using tissue samples extracted from the 58 prostates and, separately, using 227 prostate core biopsies.
  
  
  RESULTS
  HOXC6, AMACR and PCA3 expression showed the best discrimination between PCa and BPH. All three genes were previously reported as the most promising mRNA-based markers for distinguishing cancerous lesions from benign prostate lesions; however, none were sufficiently sensitive and specific to meet the criteria for a PCa diagnostic biomarker. By contrast, DNA methylation levels of the APC, TACC2, RARB, DGKZ and HES5 promoter regions achieved high discriminating sensitivity and specificity, with area under the curve (AUCs) reaching 0.95-1.0. Only a small overlap was detected between the DNA methylation levels of PCa-positive and PCa-negative needle biopsies, with AUCs ranging between 0.854 and 0.899.
  
  
  CONCLUSIONS
  DNA methylation-based biomarkers reflect the prostate malignancy and might be useful in supporting clinical decisions for suspected PCa following an initial negative prostate biopsy.
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, 01-813 Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Paziewska
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Dabrowska
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Goryca
authors.affiliation: Department of Urology, Multidisciplinary Hospital Warsaw-Miedzylesie, 04-749 Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Antoniewicz
authors.affiliation: Department of Urology, Medical Center for Postgraduate Education, 01-813 Warsaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Dobruch
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Mikula
authors.affiliation: 1] Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, 01-813 Warsaw, Poland [2] Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Jarosz
authors.affiliation: Department of Urology, Multidisciplinary Hospital Warsaw-Miedzylesie, 04-749 Warsaw, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Zapala
authors.affiliation: Department of Urology, Medical Center for Postgraduate Education, 01-813 Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Borowka
authors.affiliation: 1] Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, 01-813 Warsaw, Poland [2] Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Ostrowski
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics; D019175:DNA Methylation; D019852:Diacylglycerol Kinase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D019852:Diacylglycerol Kinase; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C555337:APC protein, human; C410333:TACC2 protein, human; C082925:retinoic acid receptor beta; C077478:HES5 protein, human; C526463:DGKZ protein, human