Pichler Renate, Fritz Josef, Heidegger Isabel, Steiner Eberhard, Culig Zoran, Klocker Helmut, Fuchs Dietmar
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.
Cancer Sci. 2017 Apr;108(4):663-670. doi: 10.1111/cas.13171. Epub 2017 Apr 12.
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.
γ-干扰素诱导的酶吲哚胺2,3-双加氧酶和GTP-环水解酶是肿瘤免疫逃逸机制中的关键因素。我们对100例新诊断的前列腺癌（PCa）患者在根治性前列腺切除术（RP）前以及RP后生化复发（BCR）时（n = 50）的血清新蝶呤水平、色氨酸分解代谢产物（色氨酸、犬尿氨酸以及犬尿氨酸与色氨酸的比值）进行了定量分析，并与49名健康男性进行了比较。同时还检测了前列腺特异性抗原（PSA）。研究了这些生物标志物对经直肠活检诊断PCa的风险、RP标本更差的组织病理学特征以及BCR后癌症特异性生存（CSS）的影响。新蝶呤（风险比[HR]，2.46；95%置信区间[CI]，1.08 - 5.61；P = 0.032）和犬尿氨酸（HR，2.93；95% CI，1.26 - 6.79；P = 0.012）水平与CSS单因素相关。在对其他生物标志物进行校正后，只有新蝶呤仍然是CSS的独立预测因子（HR，2.56；95% CI，1.07 - 6.12；P = 0.035）。只有PSA与活检诊断PCa的风险增加相关，单因素分析时（比值比，3.14；95% CI，1.68 - 5.88；P < 0.001）以及对其他生物标志物进行校正后（比值比，3.29；95% CI，1.70 - 6.35；P < 0.001）均如此。此外，只有术前PSA能够分别预测RP标本的手术切缘阳性（受试者工作特征曲线下面积[AUC] = 0.71；95% CI，0.59 - 0.82；P = 0.001）、更高的Gleason评分（AUC = 0.75；95% CI，0.66 - 0.85；P < 0.001）和前列腺外侵犯（AUC = 0.79；95% CI，0.69 - 0.88；P < 0.001）。虽然血清新蝶呤和色氨酸分解代谢产物不能被视为检测PCa或预测更差最终病理结果的生物标志物，但新蝶呤水平对于在BCR后将患者分层到不同的预后组是有用的。
