3-Dimensional profile of circulating miRNA for early cancer detection

 描述（由申请人提供）：循环中的miRNA可能是癌症的良好生物标志物，因为miRNA调节基因表达，因此与癌症的发生和发展有关。它们很容易检测，并且血液或血清采样被认为是非侵入性的，易于实施。然而，要将可重复和可靠的生物标志物应用于临床诊断，还有很长的路要走。个体之间、样品处理、miRNA提取和检测技术等中miRNA表达水平的巨大差异，所有这些都导致了不同研究小组报告的循环miRNA签名之间的极差一致性。最近发现的不同的miRNA载体，即蛋白质，高表达， 高密度脂蛋白（HDL）颗粒和外泌体在循环系统中的作用表明，可能只有一种特定类型的miRNA与癌症有关;然而，仍然不知道哪种类型的miRNA是杀手。 因此，我们建议检查的三维表达谱的miRNAs，这将提供有关的分布在不同群体的运营商之间的信息。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处理和提取的变化。通过比较从健康对照和癌症患者中收集的分布谱，将鉴定患者血清中不同类型载体内miRNA相对含量的不同变化，这将有助于癌症检测。还将鉴定用于标准化不同个体中以及在不同条件下处理和/或储存的样品中的miRNA含量的适当内部对照。此外，高度简化分级过程的微芯片装置将有助于在大量患者血清样品中进行生物标志物验证。 拟议研究的最终成果将是具体、敏感和可靠的 用于早期癌症检测的生物标志物。对这些标志物的评估也将非常简单，可以在常规的临床实验室中进行，以帮助更多的患者与癌症作斗争，并通过在早期捕获癌症发展的信号来提高生存率。

 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.