title: Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia.
abstract: BACKGROUND
  High-grade prostatic intraepithelial neoplasia (HGPIN) is a recognized precursor stage of PCa. Men who present HGPIN in a first prostate biopsy face years of active surveillance including repeat biopsies. This study aimed to identify non-invasive prognostic biomarkers that differentiate early on between indolent HGPIN cases and those that will transform into actual PCa.
  
  
  METHODS
  We measured the expression of 21 candidate mRNA biomarkers using quantitative PCR in urine sediment samples from a cohort of 90 patients with initial diagnosis of HGPIN and a posterior follow up of at least two years. Uni- and multivariate statistical analyses were applied to analyze the candidate biomarkers and multiplex models using combinations of these biomarkers.
  
  
  RESULTS
  PSMA, PCA3, PSGR, GOLM, KLK3, CDH1, and SPINK1 behaved as predictors for PCa presence in repeat biopsies. Multiplex models outperformed (AUC = 0.81-0.86) the predictive power of single genes, including the FDA-approved PCA3 (AUC = 0.70). With a fixed sensitivity of 95%, the specificity of our multiplex models was of 41-58%, compared to the 30% of PCA3. The PPV of our models (30-38%) was also higher than the PPV of PCA3 (27%), suggesting that benign cases could be more accurately identified. Applying statistical models, we estimated that 33% to 47% of repeat biopsies could be prevented with a multiplex PCR model, representing an easy applicable and significant advantage over the current gold standard in urine sediment.
  
  
  CONCLUSIONS
  Using multiplex RTqPCR-based models in urine sediment it is possible to improve the current diagnostic method of choice (PCA3) to differentiate between benign HGPIN and PCa cases.
authors.affiliation: Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Sequeiros
authors.affiliation: Department of Urology, Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Bastarós
authors.affiliation: Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Milagros
authors.initials: M
authors.lastname: Sánchez
authors.affiliation: Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Rigau
authors.affiliation: Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Melania
authors.initials: M
authors.lastname: Montes
authors.affiliation: Department of Urology, Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Placer
authors.affiliation: Department of Urology, Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Jaques
authors.initials: J
authors.lastname: Planas
authors.affiliation: Department of Pathology, Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: de Torres
authors.affiliation: Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.|Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, Barcelona, Spain.|IDIBELL- Bellvitge Biomedical Research Institute, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Reventós
authors.affiliation: Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: D Michiel
authors.initials: DM
authors.lastname: Pegtel
authors.affiliation: Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.|Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, Barcelona, Spain.
authors.forename: Andreas
authors.initials: A
authors.lastname: Doll
authors.affiliation: Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.|Department of Urology, Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Morote
authors.affiliation: Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Olivan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D001706:Biopsy; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011379:Prognosis; D019048:Prostatic Intraepithelial Neoplasia / Q000473:pathology* / Q000652:urine*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000652:urine*; D012333:RNA, Messenger / Q000652:urine; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger
keywords: HGPIN; PCa; diagnosis; repeat biopsy; urine