Extracellular vesicles as a source for non-invasive biomarkers in bladder cancer progression
Extracellular vesicles as a source for non-invasive biomarkers in bladder cancer progression
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DOI：
10.1016/j.ejps.2016.10.008
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发表时间：
2017-02-15
影响因子：
4.6
通讯作者：
Yanez-Mo, Maria
中科院分区：
文献类型：
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作者：
Andreu, Zoraida;Otta Oshiro, Renan;Yanez-Mo, Maria
膀胱癌是仅次于前列腺癌的第二大尿路恶性肿瘤。目前的诊断技术，如膀胱镜检查和活检，都是高度侵入性的，并伴随着不良的副作用。此外，目前还没有合适的生物标志物来预测复发或进展的预后。我们分析了膀胱粘膜尿路上皮肿瘤细胞释放到尿液中的微RNA(MiRNAs)和细胞外小泡(EV)蛋白的特异性成分是否能反映其病理状态。为此，我们分离了尿液中的EV，并在健康供者和低或高级别膀胱癌患者中评估了它们的蛋白质和miRNA组成。利用包含851个人类miRNAs探针的微阵列平台，我们在高级别膀胱癌尿液EV中发现了26个非调控的miRNAs，其中23个下调，3个上调。实时定量聚合酶链式反应分析表明miR-375是高级别膀胱癌的生物标志物，而miR146a可以识别低级别患者。最后，来自肿瘤患者的EV中的几个蛋白质标记物也被解除了调控。我们的数据表明，在100,000个小球中ApoB的存在是恶性肿瘤的明显标志。(C)2016爱思唯尔B.V.保留所有权利。
Bladder cancer is the second most frequent malignancy of the urinary tract after prostate cancer. Current diagnostic techniques, such as cystoscopy and biopsies are highly invasive and accompanied of undesirable side effects. Moreover, there are no suitable biomarkers for relapse or progression prognosis. We analysed whether the specific composition of microRNAs (miRNAs) and proteins of extracellular vesicles (EVs) that urothelial tumour cells of bladder mucosa release into the urine, could reflect their pathologic condition. For this purpose, urinary EVs were isolated and their protein and miRNA composition evaluated in healthy donors and low or high-grade bladder cancer patients. Using a microarray platform containing probes for 851 human miRNAs we found 26 deregulated miRNAs in high-grade bladder cancer urine EVs, from which 23 were downregulated and 3 upregulated. Real-time PCR analysis pointed to miR-375 as a biomarker for high-grade bladder cancer while miR146a could identify low-grade patients. Finally, several protein markers were also deregulated in EVs from tumour patients. Our data suggest that the presence of ApoB in the 100,000 pellet is a clear marker for malignancy. (C) 2016 Elsevier B.V. All rights reserved.