The Interferon-gamma induced enzymes indoleamine 2,3-dioxygenase and GTP-cylohydrolase are key players in tumor immune escape mechanisms. We quantified serum levels of neopterin and tryptophan breakdown (tryptophan, kynurenine and kynurenine-to-tryptophan ratio) in addition to prostate-specific antigen (PSA) in newly diagnosed prostate cancer (PCa) patients (n=100) before radical prostatectomy (RP) as well as at time of biochemical recurrence (BCR) after RP (n=50) in comparison to healthy men (n=49). Effects of biomarkers on the risk of PCa diagnosis on transrectal biopsy, worse histopathological characteristics of the RP specimens and cancer-specific survival (CSS) after BCR were investigated. Neopterin [hazard ratio (HR) = 2.46, 95% Cl: 1.08-5.61; p=0.032] and kynurenine [HR = 2.93, 95% Cl: 1.26-6.79; p=0.012] levels were univariately associated with CSS. When adjusted for other biomarkers, only neopterin remained an independent predictor of CSS [HR = 2.56, 95% Cl: 1.07-6.12; p=0.035]. Only PSA was associated with an increased risk of PCa diagnosis on biopsy, univariately [odds ratio (OR) = 3.14, 95% confidence interval (Cl): 1.68-5.88; p<0.001] as well when adjusted for other biomarkers [OR = 3.29, 95% Cl: 1.70-6.35; p<0.001]. Moreover, only preoperative PSA was able to predict positive surgical margin (AUC=0.71, 95% CI: 0.59-0.82, p=0.001), higher Gleason score (AUC=0.75, 95% CI: 0.66-0.85, p<0.001) and extraprostatic involvement (AUC=0.79, 95% CI: 0.69-0.88, p<0.001) at RP specimens, respectively. While serum neopterin and tryptophan breakdown cannot be considered as biomarkers in detecting PCa or in predicting worse final pathological findings, neopterin levels are useful for stratifying patients into different prognostic groups after BCR. This article is protected by copyright. All rights reserved.
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Cancer science. 2017 Jan 20 [Epub ahead of print]
Renate Pichler, Josef Fritz, Isabel Heidegger, Eberhard Steiner, Zoran Culig, Helmut Klocker, Dietmar Fuchs
Department of Urology, Urological Laboratory and Division of Experimental Urology., Department of Medical Statistics, Informatics and Health Economics., Division of Biological Chemistry, Biocenter, Medical University Innsbruck, Austria.