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Biomarkers for the diagnosis of prostatic inflammation in benign prostatic hyperplasia
Author(s) -
Robert Grégoire,
Smit Frank,
Hessels Daphne,
Jannink Sander,
Karthaus Herbert F.M.,
Aalders Tilly,
Jansen Kees,
de la Taille Alexandre,
Mulders Peter F.,
Schalken Jack A.
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21387
Subject(s) - hyperplasia , medicine , prostate , inflammation , prostate cancer , prostate diseases , urine , prostatic diseases , pca3 , urology , urinary system , prospective cohort study , pathology , cancer
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. Prostate 71:1701–1709, 2011. © 2011 Wiley‐Liss, Inc.