Core-Biomarker Reference Laboratory

核心生物标志物参考实验室

• 批准号: 10696080
• 负责人: OLIVER John SEMMES
• 金额: $ 9.75万
• 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/10696080
• 关键词: Acceleration; Agreement; Algorithms; BRCA2 gene; Benchmarking; Biological Assay; Biological Markers; CLIA certified; Certification; Clinical; Clinical Management; Communities; Data; Data Analyses; Data Discovery; Data Set; Development; Diagnostic; Disease; Early Detection Research Network; Early Diagnosis; Early identification; Ecosystem; Ensure; Environment; Fostering; Gene Expression; Image; Immunoassay; Individual; Indolent; Laboratories; Lesion; Life; Liquid substance; Literature; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Mass Spectrum Analysis; Methodology; Methods; Modernization; Molecular; Newly Diagnosed; Patients; Peptides; Performance; Process; Prostate; Proteins; Proteomics; Protocols documentation; Quality Control; RNA; Reproducibility; Research; Research Personnel; Resources; Risk; Route; Sensitivity and Specificity; Standardization; Structure; Talents; Technical Expertise; Techniques; Tissues; Translating; Translational Research; Translations; Tumor Tissue; Urine; Validation; Variant; Virginia; Work; biomarker development; biomarker discovery; biomarker panel; biomarker performance; biomarker validation; cancer type; candidate marker; candidate selection; clinical decision support; clinical decision-making; clinical diagnostics; clinical translation; cohort; design; diagnostic assay; disorder risk; high dimensionality; improved; laboratory development; machine learning method; men; molecular marker; multimodality; new growth; programs; protein biomarkers; proteogenomics; protocol development; risk stratification; statistical and machine learning; statistical learning; success; timeline; tool

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.

项目概要 新诊断的局限性前列腺癌临床治疗的关键挑战仍然存在 区分惰性癌症与侵袭性和危及生命的癌症。迫切需要生物标志物 识别那些患有侵袭性疾病并将受益于明确治疗的患者。我们 因此，建议应用基于蛋白质组学的互补发现方法来识别然后 验证前列腺近端液体和肿瘤组织中的分子特征，这些特征将用于准确的早期诊断 检测侵袭性前列腺癌并改善疾病风险分层。预期用途 这些生物标志物将早期识别出有升学风险的男性，并改善风险- 对他们进行分层。 我们的生物标志物开发实验室有三个目标：1) 验证我们现有的基于尿液的生物标志物 从我们自己的队列中选择的符合 ProBE 的研究中的年级进展以及 EDRN GU 升级 学习。 2) 开发和验证基于尿液和组织的生物标志物，用于 MRI“隐形”风险分层 高级别病变。 3) 开发和验证生物标志物，以对与有害物质相关的风险进行分层 种系 BRCA2 变异。 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有针对性的临床稳健检测 生物标志物面板。我们还将开发交叉引用统计严谨性的决策算法 以最佳临床表现为基准。除了这些 BCC 活动之外，我们还将开发强大的 适用于其他 EDRN BCC 和 CVC 的 PRM-MS 检测和统计上严格的决策工具。 总而言之，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。我们将通过重点关注来补充这些活动 通过培养初级研究员，促进生物标志物开发领域新型、多样化人才的成长 参与生物标志物开发的各个方面。