The EDRN Mesothelioma Biomarker Discovery Laboratory

EDRN 间皮瘤生物标志物发现实验室

• 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
• 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

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.

石棉相关的恶性肿瘤，恶性胸膜间皮瘤（MPM），往往是在晚期发现， 几乎没有生存机会的阶段。需要生物标志物来（1）确定哪些患者已经 石棉暴露（AE）（2）区分AE和非MPM恶性肿瘤与MPM患者（3） 确定哪些MPM患者早期复发或死亡的风险最高。EDRN 间皮瘤生物标志物发现实验室将完善和验证三种新的MPM血液/积液 基于标记物（FBLN 3，SOMAmer 13分类器，HMGB 1亚型），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与其他对照组分层。所有这些都在I/II期 发现研究已经产生AUC> 0.9。一种内部的、基于Luminex的新型测定（索马14 NYU MPM）由13个慢解离速率修饰的适体（SOMAmer）和新构建的FBLN 3组成 SOMAmer将使用用于 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，随后 对玛格丽特公主癌症中心提供的标本进行盲法验证。大学 夏威夷/锡达西奈医学中心，使用202纽约大学胸腔积液，将评估一个独特的，技术上 经验证的HMGB 1电喷雾离子化液相色谱串联质谱测定法 及其亚型来区分MPM与非MPM良性和恶性积液。的hmgb 1 将积液结果与使用索马14 NYU MPM确认获得的结果进行比较 队列来自圣地亚哥、智利和南格拉斯哥批准的EDRN MPM筛查项目 大学医院。最后，我们将完善和验证我们的血沉棕黄层/PBMC MPM谱的5个免疫- 在II期研究中可以区分非AE个体与AE个体与MPM的肿瘤学基因， AUC为1.0。这些研究可能会产生3种新的平台，单独或联合使用， 显著提高了MPM患者早期诊断和准确诊断机会。