高 Gleason 评分前列腺癌患者尿细胞外囊泡的蛋白质组学分析。
Proteomic analysis of urinary extracellular vesicles from high Gleason score prostate cancer.
机构信息
Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
Laboratory of Proteome Research, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
出版信息
Sci Rep. 2017 Feb 17;7:42961. doi: 10.1038/srep42961.
Extracellular vesicles (EVs) are microvesicles secreted from various cell types. We aimed to discover a new biomarker for high Gleason score (GS) prostate cancer (PCa) in urinary EVs via quantitative proteomics. EVs were isolated from urine after massage from 18 men (negative biopsy [n = 6], GS 6 PCa [n = 6], or GS 8-9 PCa [n = 6]). EV proteins were labeled with iTRAQ and analyzed by LC-MS/MS. We identified 4710 proteins and quantified 3528 proteins in the urinary EVs. Eleven proteins increased in patients with PCa compared to those with negative biopsy (ratio >1.5, p-value < 0.05). Eleven proteins were chosen for further analysis and verified in 29 independent urine samples (negative [n = 11], PCa [n = 18]) using selected reaction monitoring/multiple reaction monitoring. Among these candidate markers, fatty acid binding protein 5 (FABP5) was higher in the cancer group than in the negative group (p-value = 0.009) and was significantly associated with GS (p-value for trend = 0.011). Granulin, AMBP, CHMP4A, and CHMP4C were also higher in men with high GS prostate cancer (p-value < 0.05). FABP5 in urinary EVs could be a potential biomarker of high GS PCa.
细胞外囊泡（EVs）是各种细胞分泌的微囊泡。我们旨在通过定量蛋白质组学在尿 EVs 中发现高格里森评分（GS）前列腺癌（PCa）的新型生物标志物。从 18 名男性（阴性活检 [n=6]、GS 6 PCa [n=6]或 GS 8-9 PCa [n=6]）按摩后的尿液中分离 EVs。用 iTRAQ 标记 EV 蛋白，并用 LC-MS/MS 分析。我们在尿 EVs 中鉴定了 4710 种蛋白质和定量了 3528 种蛋白质。与阴性活检患者相比，11 种蛋白质在 PCa 患者中增加（比值>1.5，p 值<0.05）。选择 11 种蛋白质进行进一步分析，并在 29 份独立的尿液样本（阴性 [n=11]，PCa [n=18]）中使用选择反应监测/多重反应监测进行验证。在这些候选标志物中，脂肪酸结合蛋白 5（FABP5）在癌症组中高于阴性组（p 值=0.009），并且与 GS 显著相关（趋势 p 值=0.011）。颗粒蛋白、AMBP、CHMP4A 和 CHMP4C 在高 GS 前列腺癌患者中也更高（p 值<0.05）。尿 EVs 中的 FABP5 可能是高 GS PCa 的潜在生物标志物。
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