3-Dimensional profile of circulating miRNA for early cancer detection

用于早期癌症检测的循环 miRNA 的 3 维图谱

• 批准号: 8889124
• 负责人: Wenwan Zhong
• 金额: $ 33.02万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-23 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8889124
• 关键词: 3-Dimensional; Agreement; Benign; Binding; Biogenesis; Biological; Biological Assay; Biological Markers; Blood Circulation; Blood specimen; Breast Diseases; Cancer Detection; Cancer Patient; Cell Culture Techniques; Cells; Clinical; Collection; Complementary DNA; Complex; Culture Media; Data Analyses; Data Collection; Detection; Development; Devices; Diagnosis; Diagnostic Neoplasm Staging; Dimensions; Disease; Early Diagnosis; Evaluation; Field Flow Fractionation; Foundations; Fractionation; Gene Expression; Genetic Techniques; High Density Lipoproteins; Human; Individual; Individual Differences; Interdisciplinary Study; Lead; Lipoproteins; Liquid substance; Location; MLLT2 gene; Malignant Neoplasms; Medical; Methods; MicroRNAs; Molecular Profiling; Molecular Sieve Chromatography; Neoplasm Metastasis; Outcome; Patients; Pilot Projects; Process; Protein Binding; Proteins; Public Health; Relative (related person); Reporting; Reproducibility; Research; Research Personnel; Resolution; Resources; Sampling; Screening for cancer; Sensitivity and Specificity; Serum; Signal Transduction; Silicon Dioxide; Solid; Specimen; Speed; Staging; Structure; Survival Rate; System; Techniques; Testing; Transportation; Validation; Variant; base; cancer diagnosis; cancer initiation; circulating microRNA; clinical Diagnosis; cohort; data acquisition; design; effective therapy; improved; internal control; malignant breast neoplasm; miRNA expression profiling; microchip; nanofiber; operation; particle; public health relevance; research study; screening; technology development

 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.

 描述（由申请人提供）：循环 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相关。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且易于实施。然而，将可重复且可靠的生物标志物应用于临床诊断还有很长的路要走，个体之间的 miRNA 表达水平的巨大差异、样本处理、miRNA 提取和检测技术等都有助于实现这一目标。不同研究小组报告的循环 miRNA 特征之间极差的一致性 最近发现不同的 miRNA 载体，即蛋白质，高度一致。 循环系统中的密度脂蛋白 (HDL) 颗粒和外泌体表明，可能只有特定类型的 miRNA 与癌症相关；然而，目前尚不清楚哪一种是杀手类型。 miRNA 的三维表达谱，这将提供有关不同载体组中 miRNA 分布的信息，将开发一种分离方法，以快速、高通量和准确地分离与不同类型载体相关的 miRNA。这种方法将显着减少 miRNA 处理和提取的差异，通过比较从健康对照和癌症患者中收集的分布图，患者血清中不同类型载体中 miRNA 的相对含量将发生明显变化。确定了适当的内部对照，以标准化不同个体以及在不同条件下处理和/或储存的样本中的 miRNA 含量。此外，高度简化分离过程的微芯片装置也将有所帮助。具有生物标志物在大量患者血清样本中进行验证所提出的研究的最终成果将是特异性的、灵敏的和可靠的。 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足够简单，可以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，并通过捕获早期癌症发展的信号来提高生存率。