title: Biomarkers for the diagnosis of prostatic inflammation in benign prostatic hyperplasia.
abstract: BACKGROUND
  Chronic prostatic inflammation could be a central mechanism in benign prostatic hyperplasia (BPH) progression. Currently, the histological examination of prostate biopsies remains the only way to diagnose prostatic inflammation. Our objective was to find new noninvasive biomarkers for the diagnosis of prostatic inflammation.
  
  
  METHODS
  Ninety BPH samples were investigated in two steps. First, a hypothesis was generated using a profiling procedure with a panel of 96 genes on an initial set of 30 samples. Then, the candidate biomarkers were validated on a large number of samples (n = 90). Gene expression was compared with the histological prostatic inflammation score based on the density and the confluence of lymphoid nodules. Finally, protein transcripts of the candidate biomarkers were investigated in urine samples and compared with clinical data.
  
  
  RESULTS
  Of the 96 genes, nine were significantly correlated with the inflammation score on the initial set of patients. Four of them were validated on the complete set of patients: CCR7, CD40LG, CTLA4, and ICOS. ICOS and CTLA4 protein levels were readily measured in urine samples using a conventional ELISA procedure. High-ICOS expression in urine was associated with a higher post-void residual and a lower maximum urinary flow rate.
  
  
  CONCLUSIONS
  Four genes were significantly upregulated at the mRNA level in the prostate tissue of patients with severe inflammation score. Two proteins were measured in urine samples, and were associated with maximum uroflowmetry and post-void residual. A prospective clinical study is needed to confirm their clinical relevance.
authors: Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. gregoire.robert@chu-bordeaux.fr
authors: Grégoire
authors: G
authors: Robert
authors: Frank
authors: F
authors: Smit
authors: Daphne
authors: D
authors: Hessels
authors: Sander
authors: S
authors: Jannink
authors: Herbert F M
authors: HF
authors: Karthaus
authors: Tilly
authors: T
authors: Aalders
authors: Kees
authors: K
authors: Jansen
authors: Alexandre
authors: A
authors: de la Taille
authors: Peter F
authors: PF
authors: Mulders
authors: Jack A
authors: JA
authors: Schalken
mesh_terms: D015415:Biomarkers / Q000652:urine; D060908:CTLA-4 Antigen / Q000235:genetics / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D011470:Prostatic Hyperplasia / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000652:urine; D011472:Prostatitis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000652:urine; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; C515370:CCR7 protein, human; C526581:CD40LIg fusion protein; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D012333:RNA, Messenger; D054400:Receptors, CCR7; D011993:Recombinant Fusion Proteins