title: Identification of a Candidate Gene Panel for the Early Diagnosis of Prostate Cancer.
abstract: OBJECTIVE
  Serum PSA (sPSA) testing has led to the identification of patients with indolent prostate cancer, and inevitably overtreatment has become a concern. Progensa PCA3 urine testing was shown to improve the diagnosis of prostate cancer, but its diagnostic value for aggressive prostate cancer is limited. Therefore, urinary biomarkers that can be used for prediction of Gleason score ≥7 prostate cancer in biopsies are urgently needed.
  
  
  METHODS
  Using gene expression profiling data, 39 prostate cancer biomarkers were identified. After quantitative PCR analysis on tissue specimens and urinary sediments, eight promising biomarkers for the urinary detection of prostate cancer were selected (ONECUT2, HOXC4, HOXC6, DLX1, TDRD1, NKAIN1, MS4A8B, PPFIA2). The hypothesis that biomarker combinations improve the diagnostic value for aggressive prostate cancer was tested on 358 urinary sediments of an intention-to-treat cohort.
  
  
  RESULTS
  A urinary three-gene panel (HOXC6, TDRD1, and DLX1) had higher accuracy [area under the curve (AUC), 0.77; 95% confidence interval (CI), 0.71-0.83] to predict Gleason score ≥7 prostate cancer in biopsies compared with Progensa PCA3 (AUC, 0.68; 95% CI, 0.62-0.75) or sPSA (AUC, 0.72; 95% CI, 0.65-0.78). Combining the three-gene panel with sPSA further improved the predictive accuracy (AUC, 0.81; 95% CI, 0.75-0.86). The accuracy of the three-gene predictive model was maintained in subgroups with low sPSA concentrations.
  
  
  CONCLUSIONS
  The urinary three-gene panel (HOXC6, TDRD1, and DLX1) represents a promising tool to identify patients with aggressive prostate cancer, also in those with low sPSA values. The combination of the urinary three-gene panel with sPSA bears great potential for the early diagnosis of patients with clinically significant prostate cancer.
authors: Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, the Netherlands.
authors: Gisele H J M
authors: GH
authors: Leyten
authors: Noviogendix, Department of Research and Development, Nijmegen, the Netherlands.
authors: Daphne
authors: D
authors: Hessels
authors: Noviogendix, Department of Research and Development, Nijmegen, the Netherlands.
authors: Frank P
authors: FP
authors: Smit
authors: Noviogendix, Department of Research and Development, Nijmegen, the Netherlands.
authors: Sander A
authors: SA
authors: Jannink
authors: Noviogendix, Department of Research and Development, Nijmegen, the Netherlands.
authors: Hans
authors: H
authors: de Jong
authors: Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, the Netherlands. Noviogendix, Department of Research and Development, Nijmegen, the Netherlands.
authors: Willem J G
authors: WJ
authors: Melchers
authors: ZGT Hospital, Department of Urology, Hengelo, the Netherlands.
authors: Erik B
authors: EB
authors: Cornel
authors: AMC University Medical Centre, Department of Urology, Amsterdam, the Netherlands.
authors: Theo M
authors: TM
authors: de Reijke
authors: CWZ Hospital, Department of Urology, Nijmegen, the Netherlands.
authors: Henk
authors: H
authors: Vergunst
authors: St Elisabeth Hospital, Department of Urology, Tilburg, the Netherlands.
authors: Paul
authors: P
authors: Kil
authors: Scheper Hospital, Department of Urology, Emmen, the Netherlands.
authors: Ben C
authors: BC
authors: Knipscheer
authors: Radboud University Nijmegen Medical Centre, Department of Pathology, Nijmegen, the Netherlands.
authors: Christina A
authors: CA
authors: Hulsbergen-van de Kaa
authors: Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, the Netherlands.
authors: Peter F A
authors: PF
authors: Mulders
authors: Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, the Netherlands.
authors: Inge M
authors: IM
authors: van Oort
authors: Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, the Netherlands. Noviogendix, Department of Research and Development, Nijmegen, the Netherlands. jack.schalken@radboudumc.nl.
authors: Jack A
authors: JA
authors: Schalken
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D002352:Carrier Proteins / Q000235:genetics / Q000652:urine; D018797:Cell Cycle Proteins; D055088:Early Detection of Cancer; D018398:Homeodomain Proteins / Q000235:genetics / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D011804:Quinolines; D012372:ROC Curve; D014157:Transcription Factors / Q000235:genetics / Q000652:urine; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C088334:Distal-less homeobox proteins; C094289:HOXC6 protein, human; D018398:Homeodomain Proteins; D011804:Quinolines; C580566:TDRD1 protein, human; D014157:Transcription Factors; C117172:AU 006