title: A three-gene panel on urine increases PSA specificity in the detection of prostate cancer.
abstract: BACKGROUND
  Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa.
  
  
  METHODS
  We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy.
  
  
  RESULTS
  By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone.
  
  
  CONCLUSIONS
  Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy.
authors.affiliation: Research Unit in Biomedicine and Translational and Pediatric Oncology, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Rigau
authors.forename: Israel
authors.initials: I
authors.lastname: Ortega
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Mir
authors.forename: Carlos
authors.initials: C
authors.lastname: Ballesteros
authors.forename: Marta
authors.initials: M
authors.lastname: Garcia
authors.forename: Marta
authors.initials: M
authors.lastname: Llauradó
authors.forename: Eva
authors.initials: E
authors.lastname: Colás
authors.forename: Núria
authors.initials: N
authors.lastname: Pedrola
authors.forename: Melania
authors.initials: M
authors.lastname: Montes
authors.forename: Tamara
authors.initials: T
authors.lastname: Sequeiros
authors.forename: Tugce
authors.initials: T
authors.lastname: Ertekin
authors.forename: Blanca
authors.initials: B
authors.lastname: Majem
authors.forename: Jacques
authors.initials: J
authors.lastname: Planas
authors.forename: Anna
authors.initials: A
authors.lastname: Ruiz
authors.forename: Miguel
authors.initials: M
authors.lastname: Abal
authors.forename: Alex
authors.initials: A
authors.lastname: Sánchez
authors.forename: Juan
authors.initials: J
authors.lastname: Morote
authors.forename: Jaume
authors.initials: J
authors.lastname: Reventós
authors.forename: Andreas
authors.initials: A
authors.lastname: Doll
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000652:urine; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D001706:Biopsy; D005820:Genetic Testing / Q000379:methods* / Q000592:standards*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods / Q000592:standards; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000652:urine*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C479341:prostate cancer antigen 3, human; D017430:Prostate-Specific Antigen