title: Use of a combination of biomarkers in serum and urine to improve detection of prostate cancer.
abstract: OBJECTIVE
  To measure a combination of novel molecular biomarkers in urine/blood samples of consecutive patients referring lower urinary tract symptoms (LUTS) not previously diagnosed, to improve prostate cancer diagnosis.
  
  
  METHODS
  Serum and urine samples from 113 men who went consecutively to the Department of Urology of our Institution. Biomarkers analyzed were AMACR and MMP-2 levels, and GSTP1/RASSF1A methylation status, in addition to PSA levels. Sensitivity, specificity, area under the ROC (AUROC) curves, and discriminant function analysis were assessed to determine the diagnostic potential of each variable alone or in combination.
  
  
  RESULTS
  Of the patients, 30.08% had PCa and the remaining ones were tumor free. Areas under the ROC (AUROC) curves were as follows: 0.476 for PSA, 0.532 for AMACR, and 0.706 for MMP-2. Sensitivity and specificity for methylation status were 53.3 and 45.9%, respectively. The combination of these biomarkers resulted in an AUROC curve of 0.788, which significantly outperformed AUROC curves for PSA (P = 0.0033) and AMACR (P = 0.0375). Sensitivity, specificity, positive and negative predictive values for the combination of biomarkers were 57.1, 96.6, 88.9, and 82.4%, respectively.
  
  
  CONCLUSIONS
  We conclude that analysis of this biomarker combination in body fluids improves very significantly the diagnosis of PCa compared to the PSA test.
authors.affiliation: Laboratory of Novel Therapeutic Targets, Division of Oncology, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Prior
authors.forename: Francisco
authors.initials: F
authors.lastname: Guillen-Grima
authors.forename: Jose E
authors.initials: JE
authors.lastname: Robles
authors.forename: David
authors.initials: D
authors.lastname: Rosell
authors.forename: Jose M
authors.initials: JM
authors.lastname: Fernandez-Montero
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
authors.forename: Raúl
authors.initials: R
authors.lastname: Catena
authors.forename: Alfonso
authors.initials: A
authors.lastname: Calvo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000652:urine*; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000652:urine; D008745:Methylation; D008875:Middle Aged; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood* / Q000652:urine*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000652:urine; D019998:Racemases and Epimerases / Q000097:blood / Q000652:urine; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D017430:Prostate-Specific Antigen; D020778:Matrix Metalloproteinase 2; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase