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通过硫氧还蛋白还原酶水平测量氧化应激作为前列腺癌的潜在生物标志物。

Oxidative stress measured by thioredoxin reductase level as potential biomarker for prostate cancer.

机构信息

Department of Urology, Zhongnan Hospital, Wuhan University Wuhan, P. R. China.

出版信息

Am J Cancer Res. 2015 Aug 15;5(9):2788-98. eCollection 2015.

Abstract

The aims of this study were to determine if Thioredoxin reductase (TR) is detected in the serum, and to establish the sensitivity and specificity of serum TR for diagnosing prostate cancer (PC). We assessed serum TR in 380 participants in the training cohort: 160 patients with PC, 120 with benign prostatic hyperplasia and 100 healthy individuals. The validation cohort comprised 320 participants: 120 with PC, 100 with BPH and 100 healthy individuals. TR was measured in serum by ELISA by independent researchers. The patients with PC were graded using the Gleason system. Receiver operating characteristic (ROC) curves were utilized to evaluate the accuracy of biomarkers to diagnose PC. The influence of serum levels of TR on tumor grade and metastasis was performed by binary logistic regression analysis. The median levels of serum TR in PC were significantly higher than that of healthy subjects and patients with BPH (P < 0.0001). Based on the ROC curve, the optimal cutoff value of serum TR levels as an indicator for auxiliary diagnosis of PC from BPH was projected to be 8.2 U/ml, which yielded a sensitivity of 81.8% and a specificity of 68.9%, with the area under the curve at 0.862 (95% CI, 0.821-0.903). Combined model (TR and PSA) showed a significantly greater discriminatory ability as compared with those markers alone. In regression analysis, after adjusting for other significant predictors, TR remained an independent metastasis predictor with an adjusted OR of 4.99 (95% CI, 2.64-8.09). Similarly, TR also was an independent High-grade tumors (HGT) predictor with an adjusted OR of 5.15 (95% CI, 2.52-9.14). Our study has demonstrated the additional benefit of TR measurement in the diagnosis of PC in the Chinese population. Further studies of the application of TR in this region may be beneficial.

摘要

本研究旨在确定血清中是否存在硫氧还蛋白还原酶 (TR),并确定血清 TR 诊断前列腺癌 (PC) 的敏感性和特异性。我们评估了来自训练队列的 380 名参与者的血清 TR:160 名 PC 患者、120 名良性前列腺增生患者和 100 名健康个体。验证队列由 320 名参与者组成:120 名 PC 患者、100 名 BPH 患者和 100 名健康个体。TR 通过酶联免疫吸附试验(ELISA)由独立研究人员在血清中进行测量。PC 患者采用 Gleason 系统分级。受试者工作特征(ROC)曲线用于评估生物标志物诊断 PC 的准确性。通过二元逻辑回归分析评估血清 TR 水平对肿瘤分级和转移的影响。基于 ROC 曲线,将血清 TR 水平作为辅助诊断 PC 与 BPH 的最佳截断值预测为 8.2 U/ml,其敏感性为 81.8%,特异性为 68.9%,曲线下面积为 0.862(95%CI,0.821-0.903)。与单独的标志物相比,联合模型(TR 和 PSA)显示出显著更高的鉴别能力。在回归分析中,在调整其他显著预测因子后,TR 仍然是独立的转移预测因子,调整后的比值比为 4.99(95%CI,2.64-8.09)。同样,TR 也是独立的高级别肿瘤(HGT)预测因子,调整后的比值比为 5.15(95%CI,2.52-9.14)。本研究表明,TR 测量在中国人群中诊断 PC 具有额外的益处。进一步研究 TR 在该地区的应用可能有益。

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