Proteomic analysis of urinary extracellular vesicles from high Gleason score prostate cancer.
Proteomic analysis of urinary extracellular vesicles from high Gleason score prostate cancer.
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DOI：
10.1038/srep42961
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发表时间：
2017-02-17
影响因子：
4.6
通讯作者：
Nonomura N
中科院分区：
文献类型：
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作者：
Fujita K;Kume H;Matsuzaki K;Kawashima A;Ujike T;Nagahara A;Uemura M;Miyagawa Y;Tomonaga T;Nonomura N
细胞外囊泡（EV）是由各种细胞类型分泌的微囊泡。我们旨在通过定量蛋白质组学发现尿EV中高Gleason评分（GS）前列腺癌（PCa）的新生物标志物。从18名男性按摩后的尿液中分离EV（阴性活检[n = 6]，GS 6 PCa [n = 6]或GS 8-9 PCa [n = 6]）。用iTRAQ标记EV蛋白并通过LC-MS/MS分析。我们在尿EV中鉴定了4710种蛋白并定量了3528种蛋白。与活检阴性的患者相比，PCa患者中有11种蛋白质增加（比率>1.5，p值< 0.05）。选择11种蛋白质进行进一步分析，并使用选定反应监测/多反应监测在29份独立尿液样本（阴性[n = 11]，PCa [n = 18]）中进行验证。在这些候选标志物中，脂肪酸结合蛋白5（FABP 5）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、CHMP 4A和CHMP 4C在具有高GS前列腺癌的男性中也更高（p值< 0.05）。尿EVs中的FABP 5可能是高GS PCa的潜在生物标志物。
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.