title: Using gene expression from urine sediment to diagnose prostate cancer: development of a new multiplex mRNA urine test and validation of current biomarkers.
abstract: BACKGROUND
  Additional accurate non-invasive biomarkers are needed in the clinical setting to improve prostate cancer (PCa) diagnosis. Here we have developed a new and improved multiplex mRNA urine test to detect prostate cancer (PCa). Furthermore, we have validated the PCA3 urinary transcript and some panels of urinary transcripts previously reported as useful diagnostic biomarkers for PCa in our cohort.
  
  
  METHODS
  Post-prostatic massage urine samples were prospectively collected from PCa patients and controls. Expression levels of 42 target genes selected from our previous studies and from the literature were studied in 224 post-prostatic massage urine sediments by quantitative PCR. Univariate logistic regression was used to identify individual PCa predictors. A variable selection method was used to develop a multiplex biomarker model. Discrimination was measured by ROC curve AUC for both, our model and the previously published biomarkers.
  
  
  RESULTS
  Seven of the 42 genes evaluated (PCA3, ELF3, HIST1H2BG, MYO6, GALNT3, PHF12 and GDF15) were found to be independent predictors for discriminating patients with PCa from controls. We developed a four-gene expression signature (HIST1H2BG, SPP1, ELF3 and PCA3) with a sensitivity of 77% and a specificity of 67% (AUC = 0.763) for discriminating between tumor and control urines. The accuracy of PCA3 and previously reported panels of biomarkers is roughly maintained in our cohort.
  
  
  CONCLUSIONS
  Our four-gene expression signature outperforms PCA3 as well as previously reported panels of biomarkers to predict PCa risk. This study suggests that a urinary biomarker panel could improve PCa detection. However, the accuracy of the panels of urinary transcripts developed to date, including our signature, is not high enough to warrant using them routinely in a clinical setting.
authors: Laboratory and Department of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain. LMENGUAL@clinic.ub.es.|Laboratory of Urology, Hospital Clínic, Centre de Recerca Biomèdica CELLEX, office B22, C/Casanova, 143, 08036, Barcelona, Spain. LMENGUAL@clinic.ub.es.
authors: Lourdes
authors: L
authors: Mengual
authors: CIBERehd. Plataforma de Bioinformática, Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
authors: Juan José
authors: JJ
authors: Lozano
authors: Laboratory and Department of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
authors: Mercedes
authors: M
authors: Ingelmo-Torres
authors: Laboratory and Department of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
authors: Laura
authors: L
authors: Izquierdo
authors: Laboratory and Department of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
authors: Mireia
authors: M
authors: Musquera
authors: Laboratory and Department of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
authors: María José
authors: MJ
authors: Ribal
authors: Laboratory and Department of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
authors: Antonio
authors: A
authors: Alcaraz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000652:urine; D014408:Biomarkers, Tumor / Q000652:urine*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000652:urine*; D017430:Prostate-Specific Antigen / Q000652:urine; D011471:Prostatic Neoplasms / Q000473:pathology / Q000652:urine*; D012333:RNA, Messenger / Q000652:urine*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen