3-Dimensional profile of circulating miRNA for early cancer detection

 描述(申请人提供)：循环中的miRNAs可能是癌症的良好生物标志物，因为miRNAs调节基因表达，从而与癌症的发生和发展有关。它们很容易检测，对血液或血清进行采样被认为是非侵入性的，实施起来也很简单。然而，在可重复和可靠的生物标志物应用于临床诊断之前，还有很长的路要走。在个体之间、在样本处理、在miRNA提取和检测技术等方面，miRNA表达水平的巨大差异都导致了不同研究小组报告的循环miRNA签名之间的极差的一致性。最近发现的不同的miRNA载体，即蛋白质，高 循环系统中的密度脂蛋白(HDL)颗粒和外切体表明，可能只有一种特定类型的miRNAs与癌症有关；然而，目前还不知道哪种类型的miRNAs将是杀手类型。因此，我们建议研究miRNAs的三维表达谱，这将提供关于miRNAs在不同载体组中分布的信息。将开发一种分离方法，以快速、高通量和半自动的方式分离与不同类型载体相关的miRNA。这种方法将显著减少miRNA处理和提取的差异。通过比较健康对照和癌症患者的分布特征，可以识别患者血清中不同类型载体中miRNAs相对含量的明显变化，这将有助于癌症检测。还将确定在不同个体以及在不同条件下处理和/或储存的样品中使miRNA含量正常化的适当内部控制。此外，高度简化分离过程的微芯片设备将有助于在大量患者血清样本中进行生物标记物验证。拟议研究的最终成果将是具体、敏感和可靠的。 用于癌症早期检测的生物标记物。对这些标志物的评估也将足够简单，以便在常规临床实验室中进行，以帮助更多的患者与癌症作斗争，并通过在早期阶段捕获癌症发展的信号来提高存活率。

 DESCRIPTION (provided by applicant): Circulating miRNAs could be good biomarkers for cancers because miRNAs regulate gene expression and thus are related to cancer initiation and development. They are easy to detect, and sampling blood or serum is considered non-invasive and simple to implement. However, there is a long way to go before reproducible and reliable biomarkers can be applied in clinical diagnosis. Large variations in miRNA expression levels among individuals, in sample handling, in miRNA extraction and detection techniques, etc., all contribute to the extremely poor agreements between the circulating miRNA signatures reported by different research groups. The recent discovery of different miRNA carriers, i.e. proteins, high density lipoprotein (HDL) particles, and exosomes, in the circulation system suggests that maybe only a particular type of miRNAs is relevant to cancers; however, it is still not known which will be the killer type. Hence, we propose to examine the 3-dimensional expression profiles of miRNAs, which will provide information about distribution of miRNAs among different groups of carriers. A separation method will be developed to fractionate miRNAs associated with different types of carriers in a rapid, high-throughput, and semi-automatic manner. Such an approach will significantly reduce variations in miRNA handling and extraction. By comparing the distribution profiles collected from healthy controls and cancer patients, distinct changes in the relative contents of miRNAs within different types of carriers in patients' sera will be identified, which will be useful for cancer detection. Proper internal controls for normalizing miRNA contents in different individuals, and in samples handled and/or stored under different conditions will also be identified. Furthermore, a microchip device that highly simplifies the fractionation process will assist with biomarker validation in a large number of patients' sera samples. The final deliverables of the proposed research will be specific, sensitive, and reliable biomarkers for early cancer detection. Evaluation of these markers will also be simple enough to be carried out in regular clinical labs to help more patients battle with cancers and increase the survival rates by capturing the signal of cancer development at the early stage.