Enabling Metabolomics Based Biomarker Discovery Studies Using Molecular Phenotyping of Exosome-Like Vesicles
Enabling Metabolomics Based Biomarker Discovery Studies Using Molecular Phenotyping of Exosome-Like Vesicles
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DOI：
10.1371/journal.pone.0151339
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发表时间：
2016-03-14
期刊：
影响因子：
3.7
通讯作者：
Cheema, Amrita K.
中科院分区：
文献类型：
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作者：
Altadill, Tatiana;Campoy, Irene;Cheema, Amrita K.
鉴定具有临床和翻译实用性的敏感和特异性生物标志物将需要智能实验策略，这将在当前可用技术的限制范围内扩大分子测量的广度和深度。外泌体代表了一种信息丰富的基质，用于识别被认为有助于痴呆和癌症等病理学的新疾病机制。尽管已经报道了使用来自不同来源的外泌体样囊泡（ELV）的蛋白质组学和转录组学研究，但外泌体代谢组表征及其在健康和疾病中的调节仍有待阐明。在这里，我们描述了基于UPLC-ESI-MS的人血浆和细胞培养基中ELV小分子谱分析的方法。在这项研究中，我们提出的证据表明，ELV确实携带丰富的代谢组，不仅可以增加低丰度生物标志物的发现，而且还可以帮助解释疾病进展的分子基础。这种方法可以很容易地转化为其他寻求开发预测生物标志物的研究，这些生物标志物随后可以与简化的靶向方法一起使用。
Identification of sensitive and specific biomarkers with clinical and translational utility will require smart experimental strategies that would augment expanding the breadth and depth of molecular measurements within the constraints of currently available technologies. Exosomes represent an information rich matrix to discern novel disease mechanisms that are thought to contribute to pathologies such as dementia and cancer. Although proteomics and transcriptomic studies have been reported using Exosomes-Like Vesicles (ELVs) from different sources, exosomal metabolome characterization and its modulation in health and disease remains to be elucidated. Here we describe methodologies for UPLC-ESI-MS based small molecule profiling of ELVs from human plasma and cell culture media. In this study, we present evidence that indeed ELVs carry a rich metabolome that could not only augment the discovery of low abundance biomarkers but may also help explain the molecular basis of disease progression. This approach could be easily translated to other studies seeking to develop predictive biomarkers that can subsequently be used with simplified targeted approaches.