Zhang Mo, Chen Lizhu, Yuan Zhengwei, Yang Zeyu, Li Yue, Shan Liping, Yin Bo, Fei Xiang, Miao Jianing, Song Yongsheng
Urology Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
Ultrasound Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
Discov Med. 2016 Nov;22(122):281-295.
Prostate cancer (PCa) is one of the most common malignant tumors and a major cause of cancer-related death for men worldwide. The aim of our study was to identify potential non-invasive serum and expressed prostatic secretion (EPS)-urine biomarkers for accurate diagnosis of PCa. Here, we performed a combined isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to compare protein profiles using pooled serum and EPS-urine samples from 4 groups of patients: benign prostate hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), localized PCa and metastatic PCa. The differentially expressed proteins were rigorously selected and further validated in a large and independent cohort using classical ELISA and Western blot assays. Finally, we established a multiplex biomarker panel consisting of 3 proteins (serum PF4V1, PSA, and urinary CRISP3) with an excellent diagnostic capacity to differentiate PCa from BPH [area under the receiver operating characteristic curve (AUC) of 0.941], which showed an evidently greater discriminatory ability than PSA alone (AUC, 0.757) (P<0.001). Importantly, even when PSA level was in the gray zone (4-10 ng/mL), a combination of PF4V1 and CRISP3 could achieve a relatively high diagnostic efficacy (AUC, 0.895). Furthermore, their combination also had the potential to distinguish PCa from HGPIN (AUC, 0.934). Our results demonstrated that the combined application of serum and EPS-urine biomarkers can improve the diagnosis of PCa and provide a new prospect for non-invasive PCa detection.
前列腺癌（PCa）是最常见的恶性肿瘤之一，也是全球男性癌症相关死亡的主要原因。我们研究的目的是确定潜在的非侵入性血清和前列腺分泌液（EPS）-尿液生物标志物，用于准确诊断PCa。在此，我们进行了一项结合相对和绝对定量等压标签（iTRAQ）的蛋白质组学分析，以比较4组患者的血清和EPS-尿液样本的蛋白质谱：良性前列腺增生（BPH）、高级别前列腺上皮内瘤变（HGPIN）、局限性PCa和转移性PCa。对差异表达的蛋白质进行了严格筛选，并使用经典的ELISA和蛋白质印迹分析在一个大型独立队列中进一步验证。最后，我们建立了一个由3种蛋白质（血清PF4V1、PSA和尿液CRISP3）组成的多重生物标志物组合，具有出色的诊断能力，可将PCa与BPH区分开来[受试者操作特征曲线下面积（AUC）为0.941]，其鉴别能力明显高于单独的PSA（AUC，0.757）（P<0.001）。重要的是，即使PSA水平处于灰色区域（4-10 ng/mL），PF4V1和CRISP3的组合也能实现相对较高的诊断效能（AUC，0.895）。此外，它们的组合还有区分PCa与HGPIN的潜力（AUC，0.934）。我们的结果表明，血清和EPS-尿液生物标志物的联合应用可以改善PCa的诊断，并为非侵入性PCa检测提供新的前景。
