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Cancer Sci. 2017 Apr;108(4):663-670. doi: 10.1111/cas.13171. Epub 2017 Apr 12.

Predictive and prognostic role of serum neopterin and tryptophan breakdown in prostate cancer.

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Urological Laboratory and Division of Experimental Urology, Department of Urology, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
Department of Medical Statistics, Informatics and Health Economics, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
Division of Biological Chemistry, Biocenter, Medical University Innsbruck, Innsbruck, Austria.


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.


Biochemical recurrence; biomarker; neopterin; prostate cancer; tryptophan degradation

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