Core-Biomarker Development Laboratory

核心生物标志物开发实验室

• 批准号: 10696075
• 负责人: Paul Christopher Boutros
• 金额: $ 38.45万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-02 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10696075
• 关键词: Adoption; Age; Algorithms; American; Autopsy; BRCA2 gene; Behavior; Benchmarking; Biochemical; Biological Assay; Biological Markers; Biopsy; Cancer Etiology; Cessation of life; Classification; Clinical; Clinical Management; DNA Repair; Data; Data Analyses; Data Set; Defect; Detection; Diagnosis; Disease; Distant; Early Detection Research Network; Early Diagnosis; Early identification; Ecosystem; Exhibits; Fostering; Gene Expression; Genetic; Germ-Line Mutation; Incidence; Indolent; Institution; Laboratories; Lesion; Life; Liquid substance; Local Therapy; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Medical Care Costs; MicroRNAs; Modernization; Molecular; Molecular Profiling; Monitor; Morbidity - disease rate; Neoplasm Metastasis; Newly Diagnosed; Nomograms; Outcome; Pathogenicity; Pathologic; Patients; Performance; Population; Prostate; Prostatic Neoplasms; Proteins; Proteomics; Protocols documentation; Publishing; Quality of life; Radiology Specialty; Research Personnel; Risk; Site; Skin Cancer; Stratification; Talents; Tissues; Tumor Tissue; United States; Urine; Variant; Virginia; aging population; biomarker development; biomarker panel; biomarker validation; cancer diagnosis; candidate marker; cohort; cost; diagnostic biomarker; disorder risk; efficacy testing; gene repair; genetic testing; improved; innovation; laboratory development; lifetime risk; male health; men; mutant; new growth; novel; patient subsets; predictive marker; premature; protein biomarkers; proteogenomics; risk stratification; serum PSA; standard of care; synergism; tool; tumor; urinary; validation studies; variant of unknown significance

Project Summary The critical challenge in the clinical management of newly-diagnosed localized prostate cancer remains distinguishing indolent from aggressive and life-threatening cancers. Biomarkers are urgently needed to identify those patients who harbor aggressive disease and will derive benefit from definitive treatment. We therefore, propose to apply complimentary proteogenomic-based discovery approaches to identify and then validate molecular features in prostate proximal fluids and tumor tissues that will be utilized in accurate early detection of aggressive forms of prostate cancer and improve disease risk stratification. The intended use of these biomarkers will be the early identification of men at risk for grade progression and improved risk- stratification for them. We have three biomarker development laboratory aims: 1) Validate our existing urine-based biomarkers for grade progression in a ProBE-compliant study selected from our own cohorts and the EDRN GU upgrading study. 2) Develop and validate urine and tissue-based biomarkers for the risk-stratification of MRI “invisible” high-grade lesions. 3) Develop and validate biomarkers to sub-stratify risk associated with deleterious germline BRCA2 variants. Our biomarker reference laboratory will develop and validate targeted clinically robust assays for multi-protein biomarkers panels. We will also develop decision algorithms that are cross-referenced for statistical rigor and benchmarked for optimal clinical performance. In addition to these BCC activities, we will develop robust PRM-MS assays and statistically rigorous decision tools for other EDRN BCCs and CVCs. Taken together, our EDRN biomarker characterization center will be a core part of the the EDRN ecosystem. We will continue to actively participate in trans-Network activities, and to share patient cohorts, protocols, datasets and analysis approaches and expertise. We will supplement these activities by focusing on promoting the growth of new and diverse talent in biomarker development through fostering junior investigator involvement across the full spectrum of biomarker development.

项目摘要 新诊断的局限性前列腺癌的临床管理的关键挑战仍然是 区分惰性和侵袭性以及威胁生命的癌症。迫切需要生物标志物， 确定那些患有侵袭性疾病并将从明确治疗中获益的患者。我们 因此，建议应用互补的基于蛋白质组学的发现方法来识别， 验证前列腺近端液体和肿瘤组织中的分子特征， 检测前列腺癌的侵袭性形式并改善疾病风险分层。的预期用途 这些生物标志物将是早期识别男性的风险等级进展和改善的风险- 对他们来说， 我们有三个生物标志物开发实验室的目标：1）验证我们现有的基于尿液的生物标志物， 从我们自己的队列和EDRN GU升级中选择的符合ProBE的研究中的年级进展 study. 2)开发和验证基于尿液和组织的生物标志物，用于MRI“不可见”的风险分层 高级别病变3)开发和验证生物标志物，以细分与有害生物相关的风险 生殖系BRCA 2变体。 我们的生物标志物参考实验室将开发和验证针对多蛋白的临床稳健检测方法， 生物标志物组。我们还将开发决策算法，这些算法可以交叉参考统计严格性， 以最佳临床性能为基准。除了这些BCC活动，我们还将开发强大的 PRM-MS分析和其他EDRN BCC和CVC的统计学严格决策工具。 总之，我们的EDRN生物标志物表征中心将成为EDRN生态系统的核心部分。 我们将继续积极参与跨网络活动，并分享患者队列，方案， 数据集、分析方法和专业知识。我们将通过以下方式补充这些活动： 通过培养初级研究者，促进生物标志物开发领域新的多样化人才的成长 参与生物标志物开发的全方位。