Development of non-invasive biomarker discovery and diagnostics approach for bladder cancer based on urine proteome and phosphoproteome

基于尿液蛋白质组和磷酸蛋白质组的膀胱癌非侵入性生物标志物发现和诊断方法的开发

• 批准号: 10251415
• 负责人: Anton Iliuk
• 金额: $ 60万
• 依托单位: TYMORA ANALYTICAL OPERATIONS, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10251415
• 关键词: Biological Assay; Biological Markers; Blood; Cancer Detection; Cancer Diagnostics; Clinical; Collection; DNA; Data; Detection; Development; Devices; Diagnostic; Disease; Disease Progression; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; FDA approved; Feasibility Studies; Freezing; In Vitro; Liquid substance; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measurable; Methods; MicroRNAs; Monitor; Neoplasm Circulating Cells; Non-Invasive Cancer Detection; Phase; Phosphoproteins; Phosphorylation; Process; Proteins; Proteome; Proteomics; Public Health; Recovery; Reporting; Reproducibility; Research; Sampling; Small Business Innovation Research Grant; Source; Standardization; Statistical Models; Technology; Testing; Time; Tissues; Training; Translating; United States National Institutes of Health; Urine; Validation; anticancer research; base; biomarker discovery; biomarker panel; cancer biomarkers; cancer type; clinical application; cohort; cost; disease diagnosis; exosome; experimental study; extracellular vesicles; innovation; instrument; liquid biopsy; model development; novel; tumor; tumor DNA; tumor heterogeneity; urinary; virtual

PROJECT SUMMARY Profiling of Extracellular Vesicles (EV) has emerged as a highly promising field for discovery of tumor-relevant biomarkers from biofluids, such as blood, urine, CSF or others. The use of biofluid EVs offers numerous advantages in clinical setting, including non-invasive collection, a suitable sample source for longitudinal disease monitoring, better screenshot of tumor heterogeneity, higher stability and sample volumes, faster processing times, lower rejection rates and costs compared to their tissue counterpart. Despite the immense potential, the data on EV phosphoproteomes are virtually non-existent. In this NIH SBIR Fast-Track study, we will further develop a novel urine analysis platform based on EVtrap beads for complete capture of extracellular vesicles and in-house developed proteome extraction and analysis approach into highly efficient and reproducible method for discovery and detection of cancer biomarkers. We have already utilized this approach to generate a new panel of protein/phosphoprotein markers from urinary EVs for sensitive and non-invasive detection and monitoring of bladder cancer. During this project, the discovered biomarkers panel will be validated and refined to demonstrate clinical utility. The following aims will be completed in the Phase I of the proposal: Aim #1: Develop and optimize EVtrap for large-scale and high-throughput EV isolation. Aim #2: Determine the feasibility of the current bladder cancer biomarkers and refine the panel. The following aims will be completed in the Phase II of the proposal: Aim #1: Adapt EVtrap to an existing automated device for high-throughput EV capture and cargo analysis. Aim #2: Validate and standardize the final panel for clinical utility. By the completion of this project, a biomarker discovery platform from urine will be developed, and bladder cancer monitoring assay will be validated that can overcome the limitations of current approaches, and thus could have an enormous public health impact and market potential.

项目摘要 细胞外囊泡（EV）的分析已成为发现的一个高度有希望的领域 来自血液，尿液，CSF或其他生物流体的肿瘤与肿瘤相关的生物标志物。生物流体的使用 EVS在临床环境中提供了许多优势，包括非侵入性收藏 纵向疾病监测的样本源，肿瘤异质性更好的屏幕截图，较高 稳定性和样本量，处理时间更快，拒绝率和成本较低 他们的组织对应物。尽管具有巨大的潜力，但有关EV磷酸蛋白质组的数据是 实际上不存在。在这项NIH SBIR快速轨道研究中，我们将进一步发展出一种新型尿液 基于EVTRAP珠的分析平台，以完全捕获细胞外囊泡和内部 开发的蛋白质组提取和分析方法是高效且可重复的方法 用于发现和检测癌症生物标志物。我们已经利用这种方法来生成 尿路电动汽车的新蛋白/磷酸蛋白标记物，用于敏感和无创的 检测和监测膀胱癌。在这个项目中，发现的生物标志物面板将 经过验证并精制以证明临床实用性。以下目标将在 提案的第一阶段：目标＃1：开发和优化大型和高通量的EVTRAP EV隔离。目标＃2：确定当前膀胱癌生物标志物和精炼的可行性 面板。提案的第二阶段将完成以下目标：AIM＃1：适应EVTRAP 到现有的自动化设备进行高通量电动汽车捕获和货物分析。目标＃2：验证 并标准化临床实用程序的最终面板。根据该项目的完成，生物标志物 将开发尿液的发现平台，膀胱癌监测测定法 经过验证的可以克服当前方法的局限性，因此可能具有巨大的 公共卫生影响和市场潜力。