Standardized Molecular Analyses of Glioma EVs

神经胶质瘤 EV 的标准化分子分析

• 批准号: 10439719
• 负责人: Bob S Carter
• 金额: $ 60.28万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10439719
• 关键词: Address; Adoption; Age; Biological Assay; Biological Markers; Biopsy; Blood; Blood Circulation; Blood Tests; Blood specimen; CLIA certified; Cancer Detection; Cancer Diagnostics; Cells; Clinical; Collaborations; Collection; Coupled; Data; Detection; Development; Device Designs; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Marker; Elements; Ensure; Epidermal Growth Factor Receptor; General Hospitals; Genes; Genetic Status; Glioma; Goals; Heterogeneity; Histologic; Industry; Knowledge; Laboratories; Literature; Malignant Glioma; Malignant Neoplasms; Massachusetts; Measurable; Messenger RNA; Methods; Modeling; Molecular; Molecular Analysis; Monitor; Mutation; Neurosphere; Operative Surgical Procedures; Outcome; Outcomes Research; Parents; Patient-Focused Outcomes; Patients; Performance; Plasma; Population; Procedures; Proteins; Protocols documentation; Quality Control; RNA; Recurrence; Reference Standards; Reproducibility; Research; Research Design; Resources; Risk; Sampling; Sensitivity and Specificity; Series; Serum; Site; Source; Standardization; Statistical Data Interpretation; Surface Antigens; Systems Biology; Technology; Testing; Time; Tissues; Translations; Variant; Vesicle; Work; assay development; base; brain tissue; cancer biomarkers; cancer cell; candidate marker; cellular engineering; clinical care; clinically translatable; cohort; data mining; design; digital; effective therapy; exosome; extracellular; extracellular vesicles; follow-up; genetic information; genetic signature; high risk; high throughput screening; improved; innovative technologies; liquid biopsy; molecular phenotype; multidisciplinary; nanoengineering; neurosurgery; plasmonics; preclinical study; success; translational impact; tumor; tumor diagnosis

Extracellular vesicles (EVs) have emerged as a promising surrogate for tissue biopsy, potentially enabling non-invasive, real-time cancer monitoring. Most cancer cells release large numbers of EVs into circulation that carry molecular constituents reflective of the heterogeneity of the parent tumor. This project is designed to optimize a liquid biopsy to diagnose malignant glioma tumors. Currently, such tumors are diagnosed through a brain tissue biopsy which involves considerable risk for patients and doesn’t allow for longitudinal follow up of clinical care. Current EV isolation and characterization methods yield inconsistent results and render data reproducibility challenging, often leading to unpredictable conclusions. The ​goals​ of this project are to i) address variability among the different EV isolation methods and platforms currently available, and to ii) pinpoint to the “best” method to validate candidate biomarkers for glioma diagnosis. Our exceptional investigative team brings together experts in malignant glioma treatment, the field of nano-engineering, vesicular research, assay development and droplet digital PCR technology to optimize the necessary elements for the development of a blood-based assay capable of moving towards clinical settings. Through a simple blood test, clinicians will be able to diagnose, stratify and monitor a tumor without the need for tissue biopsy. Our strategic partnership with ​Exosome Diagnostics​, an industry leader in EV-based cancer diagnostics, offers us venues allowing for the translation of our findings, coupled with access to clinical grade kits, platforms and study design. The D​ epartment of Neurosurgery​ and the ​Center for Systems Biology​ at the Massachusetts General Hospital comprise multidisciplinary clinical expertise, innovative technologies and complementary resources to carry out the following translational projects: ​First,​ based on our prior kit comparison work, we have picked two top EV isolation kits and enrichment platforms to test in a series of well controlled, reference standards to determine an optimal EV isolation method. ​Second,​ we will test whether EV gene signatures can be used as biomarkers for cancer detection as well as tracking recurrence. By following quality control on device design and sample processing, accruing well-annotated patient and control samples, and performing multi site testing, we will ​ensure assay reliability and reproducibility​ to deliver clinically translatable EV diagnostics. Fourteen genes were selected through literature data mining based on the putative evidence that they can distinguish gliomas from controls. ​Finally,​ a gene’s signature with the highest sensitivity and specificity will be validated in a large cohort of patient samples. The technical and scientific outcomes of this research could have a significant ​translational impact in gliomas​, establishing a robust, highly specific assay to guide treatment decision and assess tumor recurrence.

细胞外蔬菜（EV）已成为组织活检的承诺代理 无创，实时癌症监测。大多数癌细胞将大量电动汽车释放到循环中 携带分子构成反映父肿瘤的异质性。该项目旨在 优化液体活检以诊断恶性神经胶质瘤肿瘤。目前，通过 脑组织活检，涉及患者的风险很大，不允许进行纵向随访 临床护理。当前的EV隔离和表征方法产生不一致的结果并渲染数据 可重复性挑战，通常会导致无法预测的结论。这个项目的目标是我 解决当前可用的不同EV隔离方法和平台之间的可变性，以及II） 精确指出“最佳”方法，以验证用于神经胶质瘤诊断的候选生物标志物。我们的非凡 调查团队汇集了纳米工程领域恶性神经胶质瘤治疗方面的专家 囊泡研究，测定开发和液滴数字PCR技术，以优化必要的 开发能够朝着临床环境发展的基于血液的测定的元素。通过一个 简单的血液检查，临床医生将能够诊断，分层和监测肿瘤，而无需组织 活检。我们与基于EV的癌症行业领导者外泌体诊断的战略合作伙伴关系 诊断，为我们提供允许转化我们发现的场所，并获得临床等级的访问 套件，平台和研究设计。神经外科和系统生物学中心 马萨诸塞州综合医院完整的多学科临床专业知识，创新技术和 完全资源来执行以下翻译项目：首先，基于我们先前的套件 比较工作，我们选择了两个顶级电动汽车隔离套件和富集平台来测试一系列井 受控的，确定最佳EV隔离方法的参考标准。第二，我们将测试EV是否 基因特征可以用作癌症检测和跟踪复发的生物标志物。通过关注 设备设计和样品处理的质量控制，累计宣布良好的患者和对照样品， 并进行多站点测试，我们将确保评估可靠性和可重复性以在临床上提供 可翻译的EV诊断。通过基于文献数据挖掘选择了14个基因 假定的证据表明他们可以将神经胶质瘤与对照区分开。最后，一个基因的签名最高 灵敏度和特异性将在大量患者样本中得到验证。技术和科学 这项研究的结果可能会对神经胶质瘤产生重大的翻译影响，建立强大的， 高度具体的评估以指导治疗决策和评估肿瘤复发。