Biomarker Developmental Laboratory

生物标志物发育实验室

• 批准号: 10684233
• 负责人: ARUL M CHINNAIYAN
• 金额: $ 24.44万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684233
• 关键词: Academic Medical Centers; Advanced Malignant Neoplasm; African American; Alternative Splicing; American; Biological Assay; Biological Markers; Biological Sciences; Biopsy; Clinical; Collaborations; Communities; DNA; Data; Development; Diagnosis; Diagnostic tests; Disease; ERG gene; Early Detection Research Network; Early Diagnosis; Expression Profiling; Formalin; Future; Gene Fusion; Guidelines; Health; In Situ Hybridization; Incidence; Individual; Industry; Knowledge; Laboratories; Libraries; Licensing; Malignant Neoplasms; Malignant neoplasm of prostate; Michigan; Minority Groups; Mission; Mutation; New York; Outcome; PSA screening; Paraffin Embedding; Pathology; Population; Populations at Risk; Procedures; Productivity; Prognosis; Prostate; Prostatectomy; Prostatic Diseases; RNA; RNA Splicing; Research; Sampling; Screening for Prostate Cancer; Selection for Treatments; Spices; Standardization; TMPRSS2 gene; Testing; Texas; Tissue Embedding; Tissues; Transcript; Translating; Translations; United States; Universities; Untranslated RNA; Urine; Validation; Variant; Virginia; Work; biomarker validation; cancer biomarkers; circular RNA; clinical development; clinical sequencing; cohort; commercialization; curative treatments; detection test; diagnostic biomarker; fusion gene; health care economics; improved; industry partner; insertion/deletion mutation; medical schools; men; mortality; multidisciplinary; novel diagnostics; novel marker; overtreatment; personalized predictions; personalized risk prediction; precision oncology; prognostic assays; programs; prostate cancer risk; serum PSA; shared decision making; specific biomarkers; success; transcriptome; transcriptome sequencing; transcriptomics

Project Summary/Abstract This application proposes the formation of the Michigan-Vanderbilt University Medical Center (VUMC) EDRN Biomarker Characterization Center (BCC). This BCC represents a collaborative, multi-disciplinary team of academic (University of Michigan (U-M) and VUMC) and industry (LynxDx) partners focused on discovering, developing, and scaling clinical-grade assays for the early detection of aggressive prostate cancer. Through previous EDRN efforts, our team characterized multiple important prostate cancer biomarkers, most notably the TMPRSS2-ETS gene fusions. Through collaboration with an EDRN Clinical Validation Center (CVC; Dr. Sanda PI), we developed, validated, and clinically implemented MyProstateScore (MPS), an early detection test incorporating urine quantification of two prostate cancer-specific transcripts—the TMPRSS2:ERG gene fusion and the long non-coding RNA (lncRNA) PCA3. Introduced in our CLIA laboratory, MPS informs shared decision making after PSA testing based on individualized risk predictions of aggressive prostate cancer on biopsy. Here, pairing the cancer-specific components of the MPS test with recent discovery of high-grade cancer-specific biomarkers, we outline the development, optimization, and clinical validation of the next generation of diagnostic tests – capable of reliably, selectively detecting potentially lethal cancers that stand to benefit from early curative treatment. Our Biomarker Developmental Laboratory (BDL) will employ the experimental platform, MPS-SEQ, for capture RNA-seq analysis of urine samples to detect aggressive prostate cancer transcripts, lncRNAs, circular RNAs, fusion transcripts, mutations, indels, and splice variants. Our Biomarker Reference Laboratory (BRL) will in parallel develop a clinical grade urine assay, MPS-50, for the multiplex QPCR analysis of up to 50 amplicons. While the first 50 amplicons of MPS-50 have already been nominated, future improvements of the assay content and platform will be informed by work carried out in our BDL. To fuel these studies, our BCC has identified urine biospecimen cohorts collected under rigorous standard operating procedures in compliance with PRoBE criteria including the Michigan Prostate SPORE, Emory University, the Center for Prostate Disease Research, University of Texas San Antonio Health, Eastern Virginia Medical School, and VUMC/Meharry Medical College. The overall Aims of this BCC serve to develop, assess, and optimize MPS-SEQ and MPS-50 for identifying high-grade prostate cancer in diverse at-risk populations. Our BRL will also focus on standardizing clinically-validated biomarker assays for consistent and reliable use in accordance with CLIA/CAP guidelines at the U-M Center for Translational Pathology in order to facilitate network consortium studies and at LynxDx in order to scale, commercialize, and obtain FDA approvals. As recognized by the EDRN, novel biomarkers specific for aggressive prostate cancer are urgently needed. Importantly, our mission and efforts extend beyond our BCC and prostate cancer, as we actively participate in the EDRN biomarker community and support continued collaborative efforts with other BCCs and CVCs to advance the overall EDRN mission.

项目摘要/摘要 本申请建议成立密歇根-范德比尔特大学医学中心(VUMC)EDRN 生物标志物表征中心(BCC)。此密件抄送代表了一个协作、多学科的团队 学术(密歇根大学(U-M)和VUMC)和行业(LynxDx)合作伙伴专注于发现、 为侵袭性前列腺癌的早期检测开发并扩大临床级别的检测方法。穿过 在之前的EDRN工作中，我们的团队表征了多个重要的前列腺癌生物标志物，其中最引人注目的是 TMPRSS2-ETS基因融合。通过与EDRN临床验证中心(CVC；Sanda博士)合作 PI)，我们开发、验证并在临床上实施了MyProstateScore(MPS)，这是一种早期检测测试 两种前列腺癌特异性转录本的尿定量--TMPRSS2：ERG基因融合 和长的非编码RNA(LncRNA)PCA3。在我们的CLIA实验室引入，MPS通知共同决定 根据活检时侵袭性前列腺癌的个体化风险预测进行PSA检测后进行。这里, 将MPS检测的癌症特异性成分与最近发现的高级别癌症特异性配对 生物标志物，我们概述了下一代诊断的开发、优化和临床验证 测试-能够可靠地、选择性地检测到可能致命的癌症，这些癌症有望从早期治疗中受益 治疗。我们的生物标记物开发实验室(BDL)将采用实验平台MPS-SEQ， 用于捕获尿样的RNA-seq分析以检测侵袭性前列腺癌转录本、lncRNA、 环状RNA、融合转录本、突变、内切和剪接变异体。我们的生物标记物参考实验室 (BRL)将同时开发临床级别的尿液分析MPS-50，用于多达50个的多重QPCR分析 扩音器。虽然MPS-50的第一批50个扩增片段已经被提名，但未来对 化验内容和平台将通过在我们的BDL中开展的工作来通知。为了推动这些研究，我们的BCC已经 根据严格的标准操作程序收集的经鉴定的尿液生物检疫样本 调查标准包括密歇根前列腺癌孢子、埃默里大学、前列腺病中心 德克萨斯大学圣安东尼奥分校、东弗吉尼亚医学院和VUMC/Meharry的研究 医学院。本BCC的总体目标是开发、评估和优化MPS-SEQ和MPS-50 用于在不同的高危人群中识别高级别前列腺癌。我们的BRL还将专注于标准化 经过临床验证的生物标记物分析，符合CLIA/CAP指南的一致和可靠使用，网址为 U-M翻译病理学中心，以促进网络联盟的研究，并在LynxDx 以扩大规模、商业化并获得FDA的批准。根据EDRN的认识，新的生物标记物特异性 对于侵袭性前列腺癌是迫切需要的。重要的是，我们的使命和努力超越了密件抄送。 和前列腺癌，因为我们积极参与EDRN生物标记物社区并继续支持 与其他BCC和CVC合作，推进EDRN的整体任务。