Predictive and prognostic role of serum neopterin and tryptophan breakdown in prostate cancer. Issue 4 (12th April 2017)

• Record Type: Journal Article
• Authors: Pichler, Renate; Fritz, Josef; Heidegger, Isabel; Steiner, Eberhard; Culig, Zoran; Klocker, Helmut; Fuchs, Dietmar
• Is Part Of: Cancer science. Volume 108:Issue 4(2017)
• Page Start: 663
• Page End: 670
• Publication Date: 2017-04-12
• Subjects: Biochemical recurrence -- biomarker -- neopterin -- prostate cancer -- tryptophan degradation; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13171
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : Accelerated neopterin and tryptophan breakdown seems to play an important role regarding prostate carcinogenesis, with the highest levels in patients with biochemical recurrence after radical prostatectomy. Neopterin was the only independent prognostic factor for cancer‐specific survival after biochemical recurrence. These data may support the recommendation of neopterin measurement in making decision for further oncologic treatment strategies and in monitoring patients during therapy following biochemical recurrence.