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.

细胞外囊泡（EV）已成为组织活检的有前途的替代品，有可能使 非侵入性实时癌症监测 大多数癌细胞会释放大量 EV 进入循环系统。 携带反映母体肿瘤异质性的分子成分。 优化液体活检来诊断恶性神经胶质瘤目前，此类肿瘤是通过以下方式诊断的。 脑组织活检对患者来说存在相当大的风险，并且不允许进行纵向随访 当前的 EV 隔离和表征方法产生不一致的结果并呈现数据。 再现性具有挑战性，通常会导致不可预测的结论。该项目的目标是 i) 解决当前可用的不同 EV 隔离方法和平台之间的差异，以及 ii) 找出验证神经胶质瘤诊断候选生物标志物的“最佳”方法。 研究小组汇集了恶性胶质瘤治疗、纳米工程领域的专家， 囊泡研究、检测开发和液滴数字 PCR 技术，以优化必要的 开发基于血液的测定能够走向临床环境的要素。 简单的血液测试，冠军将能够诊断、分层和监测肿瘤，而不需要组织 我们与基于 EV 的癌症行业领导者 Exosome Diagnostics 建立战略合作伙伴关系。 诊断，为我们提供了可以转化我们的发现以及获得临床级别的场所 套件、平台和研究设计。 马萨诸塞州总医院拥有多学科临床专业知识、创新技术和 补充资源来开展以下转化项目：​首先，​基于我们之前的套件 对比工作中，我们挑选了两款顶级的EV隔离套件和富集平台在一系列井中进行测试 受控的参考标准来确定最佳的 EV 隔离方法第二，我们将测试 EV 是否有效。 基因特征可用作癌症检测和跟踪复发的生物标志物。 设备设计和样品处理的质量控制，积累注释良好的患者和对照样品， 并进行多站点测试，我们将确保临床交付的检测可靠性和再现性 基于文献数据挖掘，选择了14个可翻译的EV诊断基因。 推定证据表明他们可以将神经胶质瘤与对照区分开来。​最后，​具有最高的基因特征。 敏感性和特异性将在大量患者样本中得到验证。 这项研究的结果可能会对神经胶质瘤产生重大的转化影响，建立一个强大的、 高度特异性的测定来指导治疗决策和评估肿瘤复发。