Identification of prostate cancer biomarkers in urinary exosomes.
Identification of prostate cancer biomarkers in urinary exosomes.
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DOI：
10.18632/oncotarget.4851
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发表时间：
2015-10-06
期刊：
影响因子：
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通讯作者：
Llorente A
中科院分区：
文献类型：
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作者：
Øverbye A;Skotland T;Koehler CJ;Thiede B;Seierstad T;Berge V;Sandvig K;Llorente A
自从从生物液中分离出的外切体中可以发现肿瘤特异性分子以来，外切体最近被认为是一种新的非侵袭性癌症生物标志物来源。我们在此利用质谱仪研究了尿外切体的蛋白质组，以确定前列腺癌患者与健康男性对照组相比差异表达的蛋白质。总共分析了15例正常对照和16例前列腺癌患者的尿液外切体。重要的是，246种蛋白质在两组中有差异表达。这些蛋白中的大多数(221)在前列腺癌患者的外切体中上调。根据特定的标准对这些蛋白质进行分析，以创建包含37种蛋白质的焦点列表。在100%的特异度下，这些蛋白质中有17个的个体敏感性超过60%。尽管其中几种蛋白质作为单独的生物标志物显示出对前列腺癌的高度敏感性和特异性，但在多组试验中结合它们有可能完全区分前列腺癌和非疾病对照。跨膜蛋白256(TM256；17号染色体开放阅读框61)的敏感性最高，为94%。LAMTOR蛋白对患者样本也有明显的富集性和很高的特异性。TM256和LAMTOR1可将灵敏度提高到100%。其他重要的蛋白质包括V型质子ATPase 16 kDa蛋白脂亚单位(VATL)、脂肪生成调节因子(ADIRF)以及几个Rab类成员和蛋白酶体蛋白。总之，这项研究清楚地表明了尿外切体在前列腺癌诊断和临床治疗中的潜力。
Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer.