Virginia-UCLA-Toronto Biomarker Characterization Center

弗吉尼亚-加州大学洛杉矶分校-多伦多生物标志物表征中心

• 批准号: 10696069
• 负责人: Paul Christopher Boutros
• 金额: $ 82.73万
• 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/10696069
• 关键词: Acceleration; Address; Algorithms; BRCA2 Mutation; BRCA2 gene; Benchmarking; Biological Assay; Biological Markers; Biopsy; Biopsy Specimen; Characteristics; Clinical; Clinical Management; Communication; Data Analyses; Data Science; Data Set; Decision Making; Diagnosis; Disease; Disease Progression; Early Detection Research Network; Early Diagnosis; Early identification; Ecosystem; Elements; Eligibility Determination; Environment; Equipoise; Fostering; Gene Family; Goals; Health; Heterogeneity; Individual; Indolent; Intervention; Laboratories; Lesion; Life; Liquid substance; Local Therapy; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Mass Spectrum Analysis; Molecular; Neoplasm Metastasis; Newly Diagnosed; Operative Surgical Procedures; Outcome; Pathologist; Patients; Performance; Phase; Process; Prostate; Protocols documentation; Qualifying; Radiation therapy; Recommendation; Research; Research Personnel; Risk; Risk Assessment; Selection for Treatments; Stratification; Subcategory; Surveillance Program; Talents; Tissues; Tumor Tissue; United States; Urine; Validation; Variant; Virginia; algorithm development; assay development; biomarker development; biomarker identification; biomarker panel; biomarker validation; clinical care; cohort; differential expression; disorder risk; early detection biomarkers; experience; high risk; improved; inter-institutional; laboratory development; men; multimodality; new growth; novel; personalized intervention; programs; protein biomarkers; proteogenomics; risk stratification; tissue biomarkers; tool; translational pipeline; tumor

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临床处理的关键挑战仍然存在 将惰性癌症与侵袭性和危及生命的癌症区分开来。迫切需要生物标志物来 确定哪些患者患有侵袭性疾病，并将从明确的治疗中受益。我们 因此，建议应用基于蛋白质基因组学的互补发现方法来识别并随后 验证前列腺近端液和肿瘤组织的分子特征，以便在准确的早期应用 检测侵袭性前列腺癌，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有晋升风险和改善风险的男性- 对他们进行分层。 我们有三个生物标记物开发实验室目标：1)验证我们现有的尿液生物标记物 从我们自己的队列和EDRN GU升级中选择的符合探针的研究中的等级进步 学习。2)开发和验证尿液和组织为基础的生物标记物，用于核磁共振“隐形”的风险分层 高级别病变。3)开发和验证生物标记物，以细分有害风险 生殖系BRCA2变异体。 我们的生物标记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可靠分析方法。 生物标记物板。我们还将开发相互参考的决策算法，以提高统计的严密性和 以最佳临床表现为基准。除了这些密件抄送活动外，我们还将发展强大的 PRM-MS分析和其他EDRN BCC和CVC的统计严格的决策工具。 综上所述，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。我们将通过关注以下内容来补充这些活动 培养初级调查员促进生物标志物开发新的多元化人才的成长 参与生物标记物开发的全过程。

项目成果

promor: a comprehensive R package for label-free proteomics data analysis and predictive modeling.

• DOI: 10.1093/bioadv/vbad025
• 发表时间: 2023
• 期刊: Bioinformatics advances

Site-Specific Intact N-Linked Glycopeptide Characterization of Prostate-Specific Membrane Antigen from Metastatic Prostate Cancer Cells.

• DOI: 10.1021/acsomega.2c02265
• 发表时间: 2022-08-30
• 期刊: ACS OMEGA
• 影响因子: 4.1
• 作者: Mackay, Stephen;Hitefield, Naomi L.;Oduor, Ian O.;Roberts, Autumn B.;Burch, Tanya C.;Lance, Raymond S.;Cunningham, Tina D.;Troyer, Dean A.;Semmes, Oliver J.;Nyalwidhe, Julius O.
• 通讯作者: Nyalwidhe, Julius O.

Optimization of small extracellular vesicle isolation from expressed prostatic secretions in urine for in-depth proteomic analysis.

• DOI: 10.1002/jev2.12184
• 发表时间: 2022-03
• 期刊: Journal of extracellular vesicles
• 影响因子: 16
• 作者: Correll VL;Otto JJ;Risi CM;Main BP;Boutros PC;Kislinger T;Galkin VE;Nyalwidhe JO;Semmes OJ;Yang L
• 通讯作者: Yang L