title: Predictive and prognostic role of serum neopterin and tryptophan breakdown in prostate cancer.
abstract: The γ-interferon-induced enzymes indoleamine 2,3-dioxygenase and GTP-cyclohydrolase 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% confidence interval [CI], 1.08-5.61; P = 0.032) and kynurenine (HR, 2.93; 95% CI, 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% CI, 1.07-6.12; P = 0.035). Only PSA was associated with an increased risk of PCa diagnosis on biopsy, univariately (odds ratio, 3.14; 95% CI, 1.68-5.88; P < 0.001) as well when adjusted for other biomarkers (odds ratio, 3.29; 95% CI, 1.70-6.35; P < 0.001). Moreover, only preoperative PSA was able to predict positive surgical margin (area under the receiver operating characteristic curve [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. Although 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.
authors.affiliation: Urological Laboratory and Division of Experimental Urology, Department of Urology, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Renate
authors.initials: R
authors.lastname: Pichler
authors.affiliation: Department of Medical Statistics, Informatics and Health Economics, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Fritz
authors.affiliation: Urological Laboratory and Division of Experimental Urology, Department of Urology, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Isabel
authors.initials: I
authors.lastname: Heidegger
authors.affiliation: Urological Laboratory and Division of Experimental Urology, Department of Urology, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Steiner
authors.affiliation: Urological Laboratory and Division of Experimental Urology, Department of Urology, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Culig
authors.affiliation: Urological Laboratory and Division of Experimental Urology, Department of Urology, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Klocker
authors.affiliation: Division of Biological Chemistry, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D006801:Humans; D053208:Kaplan-Meier Estimate; D007737:Kynurenine / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019798:Neopterin / Q000097:blood*; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011184:Postoperative Period; D011237:Predictive Value of Tests; D057234:Preoperative Period; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D012372:ROC Curve; D014364:Tryptophan / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan; D017430:Prostate-Specific Antigen
keywords: Biochemical recurrence; biomarker; neopterin; prostate cancer; tryptophan degradation