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.

项目总结/摘要 本申请提出了组建里根-范德比尔特大学医学中心（VUMC）EDRN的建议 生物标志物表征中心（BCC）。这个BCC代表了一个协作的多学科团队， 学术（密歇根大学（U-M）和VUMC）和行业（LynxDx）合作伙伴专注于发现， 开发和扩展临床级检测方法，用于早期检测侵袭性前列腺癌。通过 在之前的EDRN工作中，我们的团队描述了多种重要的前列腺癌生物标志物，最值得注意的是 TMPRSS 2-ETS基因融合体。通过与EDRN临床验证中心（CVC; Dr. Sanda）合作， PI），我们开发，验证，并在临床上实施MyProstateScore（MPS），一种早期检测测试 结合两种前列腺癌特异性转录物的尿液定量-TMPRSS 2：ERG基因融合 和长链非编码RNA（lncRNA）PCA 3。在我们的CLIA实验室推出，MPS告知共享决策 PSA检测后根据活检中侵袭性前列腺癌的个性化风险预测进行。在这里， 将MPS测试的癌症特异性成分与最近发现的高级别癌症特异性成分进行配对， 生物标志物，我们概述了下一代诊断的发展，优化和临床验证 测试-能够可靠地，选择性地检测可能致命的癌症，这些癌症可以从早期治疗中受益 治疗我们的生物标志物开发实验室（BDL）将采用实验平台MPS-SEQ， 用于尿液样品的捕获RNA-seq分析以检测侵袭性前列腺癌转录物，lncRNA， 环状RNA、融合转录物、突变、插入缺失和剪接变体。我们的生物标志物参考实验室 (BRL)将同时开发一种临床级尿液检测试剂MPS-50，用于多达50 扩增子。虽然MPS-50的前50个扩增子已经被提名，但未来对MPS-50扩增子的改进还有待进一步研究。 检测内容和平台将通过我们的BDL中进行的工作进行通知。为了推动这些研究，我们的BCC已经 按照严格的标准操作规程采集的已确定尿液生物标本队列， PRoBE标准包括密歇根州前列腺SPORE、埃默里大学、前列腺疾病中心 研究，德克萨斯大学圣安东尼奥健康，东弗吉尼亚医学院，和VUMC/Meharry 医学院该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 临床验证的生物标志物检测，可根据CLIA/CAP指南一致可靠地使用， 密歇根大学转化病理学中心，以促进网络联盟的研究和LynxDx在 以扩大规模，商业化，并获得FDA的批准。正如EDRN所认识到的，新的生物标志物特异性 迫切需要治疗侵袭性前列腺癌。重要的是，我们的使命和努力不仅限于BCC 和前列腺癌，因为我们积极参与EDRN生物标志物社区，并继续支持 与其他BCC和CVC合作，推进EDRN的整体使命。