The EDRN Mesothelioma Biomarker Discovery Laboratory

EDRN 间皮瘤生物标志物发现实验室

基本信息

批准号：
9751814
负责人：
HARVEY Ira PASS
金额：
$ 47.97万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-20 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751814
关键词：
Adjuvant Therapy Archives Asbestos Benign Pleural Mesothelioma Biological Assay Biological Markers Blinded Blood Cancer Center Cessation of life Chile Chronic Development Diagnosis Diagnostic Disease Early Detection Research Network Early Diagnosis Electrospray Ionization Enzyme-Linked Immunosorbent Assay Exposure to Fiber Future Gene Expression Genes Genetic Transcription Goals HMGB1 gene Hawaii Immune Immunooncology Individual Investigation Laboratories Lead Liquid Chromatography Liquid substance Malignant - descriptor Malignant Neoplasms Malignant Pleural Mesothelioma Mass Spectrum Analysis Measures Medical center Mesothelioma Monitor Mutation Non-Malignant Occupational Exposure Operative Surgical Procedures Oxides Patient Monitoring Patients Peripheral Blood Mononuclear Cell Phase Plasma Pleural effusion disorder Population Predisposition Prognostic Marker Protein Isoforms Proteomics Recording of previous events Recurrence Retrospective cohort Risk S1-5 protein Sensitivity and Specificity Specimen Technology Testing Thoracic Surgical Procedures Time Tumor Debulking Universities University Hospitals Validation aptamer base biomarker discovery carcinogenicity cohort diagnostic biomarker effusion high risk improved nano-string neuronal cell body novel phase 2 study prognostic prognostic signature prospective screening screening program tandem mass spectrometry tool

项目摘要

The asbestos-related malignancy, malignant pleural mesothelioma (MPM), is often detected in late stages with little chance for survival. Biomarkers are needed to (1)determine which patients have been asbestos exposed (AE) (2) distinguish AE and non-MPM malignancies from MPM patients and (3) determine which MPM patients are at highest risk for early recurrence or death. The EDRN Mesothelioma Biomarker Discovery Laboratory will refine and validate three novel MPM blood/effusion based markers (FBLN3, SOMAmer 13 classifier, HMGB1 Isoforms) and investigate whether immune- oncologic gene expression differences in the cellular component of the circulating blood microenvironment can stratify AE and MPM from other control cohorts. All of these in Phase I/II discovery studies have yielded AUCs > 0.9. An in-house, novel Luminex based assay (Soma 14 NYU MPM) consisting of 13 slow-off-rate-modified-aptamers (SOMAmers) and a newly constructed FBLN3 SOMAmer will be assembled and technically validated using identical specimens that were used to discover these 14 analytes. Diagnostic and prognostic capabilities in both plasma and pleural effusion will be performed with healthy, non-AE exposed, AE, MPM, and non- MPM cancer cohorts, followed by a blinded validation in specimens provided by the Princess Margaret Cancer Center. The University of Hawaii/Cedar Sinai Medical Center, using 202 NYU pleural effusions, will evaluate a unique, technically validated, electrospray ionization liquid chromatography tandem mass spectrometry assay for HMGB1 and its isoforms to differentiate MPM from non-MPM benign and malignant effusions. The HMGB1 effusion results will be compared to those obtained with the Soma 14 NYU MPM using validation cohorts from an approved EDRN MPM screening program in Santiago, Chile and South Glasgow University Hospital. Finally we will refine and validate our buffy coat/PBMC MPM profile of 5 immuno- oncology genes which in Phase II studies can separate non AE individuals vs AE individuals vs MPM with AUCs of 1.0. These studies could lead to 3 novel platforms which individually or combined could significantly improve chances for early diagnosis and accurate prognostication of patients with MPM.

与石棉相关的恶性肿瘤，即恶性胸膜间皮瘤 (MPM)，通常在晚期才被发现。生存机会很小的阶段。需要生物标志物来 (1) 确定哪些患者已接受过治疗石棉暴露 (AE) (2) 将 AE 和非 MPM 恶性肿瘤与 MPM 患者区分开来，以及 (3) 确定哪些 MPM 患者早期复发或死亡的风险最高。欧洲发展研究网络间皮瘤生物标志物发现实验室将完善和验证三种新型 MPM 血液/积液基于标记（FBLN3、SOMAmer 13 分类器、HMGB1 异构体）并研究是否免疫- 循环血液细胞成分中的肿瘤基因表达差异微环境可以将 AE 和 MPM 与其他对照组进行分层。所有这些都在第一/第二阶段发现研究的 AUC > 0.9。一种内部新颖的基于 Luminex 的测定（Soma 14 NYU MPM）由 13 个慢解速率修饰适体 (SOMAmers) 和一个新构建的 FBLN3 组成 SOMAmer 将使用相同的样本进行组装和技术验证发现这 14 种分析物。血浆和胸腔积液的诊断和预后能力将在健康、非 AE 暴露、AE、MPM 和非 MPM 癌症队列中进行，然后对玛格丽特公主癌症中心提供的样本进行盲法验证。大学夏威夷/雪松西奈医疗中心将使用 202 份纽约大学胸腔积液来评估一项独特的技术经验证的 HMGB1 电喷雾电离液相色谱串联质谱测定及其亚型以区分 MPM 与非 MPM 良性和恶性积液。 HMGB1 将使用验证将积液结果与 Soma 14 NYU MPM 获得的结果进行比较来自智利圣地亚哥和南格拉斯哥经批准的 EDRN MPM 筛查计划的队列大学医院。最后，我们将完善并验证 5 个免疫组的血沉棕黄层/PBMC MPM 谱在 II 期研究中可以区分非 AE 个体、AE 个体和 MPM 的肿瘤基因 AUC 为 1.0。这些研究可能会产生 3 个新颖的平台，它们单独或组合起来可以显着提高 MPM 患者的早期诊断和准确预后的机会。