title: Stratification of aggressive prostate cancer from indolent disease-Prospective controlled trial utilizing expression of 11 genes in apparently benign tissue.
abstract: The aim of the study was to evaluate the diagnostic power of molecular markers in men with a clinical suspicion of prostate cancer (PCa) using apparently benign areas as targeted by magnetic resonance imaging (MRI).
  
  
  
  In the study, 99 consecutive men with clinical suspicion of PCa in a prospective controlled trial (IMPROD, NCT01864135) were included. In addition to 12-core systematic and MRI-targeted biopsies, cores from normal-appearing prostate areas, based on clinical examination, ultrasound, and biparametric prostate MRI, were obtained. The RNA transcript levels of ACSM1, AMACR, CACNA1D, DLX1, KLK3, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 were measured with quantitative reverse-transcription polymerase chain reaction.
  
  
  
  Of the 99 men, 69 were diagnosed with PCa, 31 with primary Gleason pattern 3 and 38 with primary Gleason 4 or 5. TDRD1 messenger RNA (mRNA) levels were 1.3 times higher (P = 0.029) and the presence of TMPRSS2-ERG mRNAs more frequent in biopsies from men diagnosed with PCa (27/69, 39%) than in men without (5/30, 16%) (P = 0.035). The 2 markers identified aggressive PCa defined as Gleason sum≥7 at biopsy: median TDRD1 mRNA level was 1.4 higher (P = 0.005) and TMPRSS2-ERG expression more frequent (P<0.001) in high-grade cancer. A multivariate analysis of mRNA expression of 11 candidate genes combined with KLK3, serum prostate-specific antigen (PSA), percentage-free PSA, and prostate volume improved the discrimination between aggressive and nonaggressive PCa (area under the curve = 0.77) compared with the use of the candidate genes or clinical parameters alone. However, serum PSA, percentage-free PSA, and prostate volume resulted in the best discrimination between non-organ-confined PCa (T3) from organ-confined PCa (T2) and healthy prostate (area under the curve = 0.86).
  
  
  
  Of the 11 studied genes, TDRD1 and TMPRSS2-ERG were able to statistically significantly differentiate men with PCa from men without it as single markers. However, a multivariate analysis using 15 features outperformed each individual marker in identifying aggressive PCa.
authors: Department of Biotechnology, University of Turku, Turku, Finland. Electronic address: saeali@utu.fi.
authors: Saeid
authors: S
authors: Alinezhad
authors: Department of Biotechnology, University of Turku, Turku, Finland.
authors: Riina-Minna
authors: RM
authors: Väänänen
authors: Department of Biotechnology, University of Turku, Turku, Finland.
authors: Terhi
authors: T
authors: Tallgrén
authors: Department of Information Technology, University of Turku, Turku, Finland; Department of Diagnostic Radiology, University of Turku, Finland.
authors: Ileana Montoya
authors: IM
authors: Perez
authors: Department of Diagnostic Radiology, University of Turku, Finland.
authors: Ivan
authors: I
authors: Jambor
authors: Department of Diagnostic Radiology, University of Turku, Finland; Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland.
authors: Hannu
authors: H
authors: Aronen
authors: Department of Urology, Turku University Hospital, Turku, Finland.
authors: Esa
authors: E
authors: Kähkönen
authors: Department of Urology, Turku University Hospital, Turku, Finland.
authors: Otto
authors: O
authors: Ettala
authors: Department of Urology, Turku University Hospital, Turku, Finland.
authors: Kari
authors: K
authors: Syvänen
authors: Turku Centre for Biotechnology and Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.
authors: Matthias
authors: M
authors: Nees
authors: Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
authors: Markku
authors: M
authors: Kallajoki
authors: Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
authors: Pekka
authors: P
authors: Taimen
authors: Department of Urology, Turku University Hospital, Turku, Finland.
authors: Peter J
authors: PJ
authors: Boström
authors: Department of Biotechnology, University of Turku, Turku, Finland.
authors: Kim
authors: K
authors: Pettersson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C580566:TDRD1 protein, human; C515553:TMPRSS2-ERG fusion protein, human; D017430:Prostate-Specific Antigen
keywords: Biomarker; Field cancerization effect; Gene expression; Prostate cancer; qRT-PCR