Serum quantitative proteomic analysis reveals potential zinc-associated biomarkers for nonbacterial prostatitis
Serum quantitative proteomic analysis reveals potential zinc-associated biomarkers for nonbacterial prostatitis
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血清定量蛋白质组学分析揭示了非细菌性前列腺炎的潜在锌相关生物标志物
作者：
Yang Xiaoli;Li Hongtao;Zhang Chengdong;Lin Zhidi;Zhang Xinhua;Zhang Youjie;Yu Yanbao;Liu Kun;Li Muyan;Zhang Yuening;Lv Wenxin;Xie Yuanliang;Lu Zheng;Wu Chunlei;Teng Ruobing;Lu Shaoming;He Min;Mo Zengnan
背景：前列腺炎是困扰成年男性最常见的泌尿系统疾病之一。非细菌性前列腺炎占病例的90-95%，其病因和发病机制在很大程度上是未知的。由于血清蛋白通常表明患者的整体病理状态，我们假设可以通过比较非细菌性前列腺炎患者和非细菌性前列腺炎患者的血清蛋白质组来确定前列腺炎的蛋白质生物标志物。方法所有未经处理的样本均来自防城港地区男性健康与检查调查（FAMHES）的调查对象。我们对四组精心挑选的患者（n = 10/组）的血清样本进行了分析，这些患者代表了不同类别的非细菌性前列腺炎（IIIa， IIIb和IV），并使用基于质谱的4 - plex iTRAQ蛋白质组学方法匹配健康对照。160余份样品经ELISA验证。结果共鉴定出69个蛋白。其中，在IIIa、IIIb和IV类前列腺炎中分别鉴定出42、52和37种差异表达蛋白。这19种常见蛋白与免疫防御、离子结合、转运和蛋白水解有关。两种锌结合蛋白，超氧化物歧化酶3 （SOD3）和碳酸酐酶I (CA1)，在所有类型的前列腺炎中都明显高于对照组。受试者工作特征曲线估计CA1和SOD3检测非细菌性前列腺炎的敏感性分别为50.4%和68.1%，特异性分别为92.1%和83.8%。血清CA1浓度与表达的前列腺分泌物中锌浓度呈负相关。结论SOD3和CA1是非细菌性前列腺炎的潜在诊断标志物，但还需要进一步的大规模研究。非细菌性前列腺炎发病机制的分子图谱可能为发现新的治疗方法奠定基础。中华医学杂志（英文版），2015。©2015 Wiley期刊公司
BACKGROUNDProstatitis is one of the most common urological problems afflicting adult men. The etiology and pathogenesis of nonbacterial prostatitis, which accounts for 90–95% of cases, is largely unknown. As serum proteins often indicate the overall pathologic status of patients, we hypothesized that protein biomarkers of prostatitis might be identified by comparing the serum proteomes of patients with and without nonbacterial prostatitis.METHODSAll untreated samples were collected from subjects attending the Fangchenggang Area Male Health and Examination Survey (FAMHES). We profiled pooled serum samples from four carefully selected groups of patients (n = 10/group) representing the various categories of nonbacterial prostatitis (IIIa, IIIb, and IV) and matched healthy controls using a mass spectrometry‐based 4‐plex iTRAQ proteomic approach. More than 160 samples were validated by ELISA.RESULTSOverall, 69 proteins were identified. Among them, 42, 52, and 37 proteins were identified with differential expression in Category IIIa, IIIb, and IV prostatitis, respectively. The 19 common proteins were related to immunity and defense, ion binding, transport, and proteolysis. Two zinc‐binding proteins, superoxide dismutase 3 (SOD3), and carbonic anhydrase I (CA1), were significantly higher in all types of prostatitis than in the control. A receiver operating characteristic curve estimated sensitivities of 50.4 and 68.1% and specificities of 92.1 and 83.8% for CA1 and SOD3, respectively, in detecting nonbacterial prostatitis. The serum CA1 concentration was inversely correlated to the zinc concentration in expressed‐prostatic secretions.CONCLUSIONSOur findings suggest that SOD3 and CA1 are potential diagnostic markers of nonbacterial prostatitis, although further large‐scale studies are required. The molecular profiles of nonbacterial prostatitis pathogenesis may lay a foundation for discovery of new therapies.Prostate 75:1538–1555, 2015. © 2015 Wiley Periodicals, Inc.