The EDRN Mesothelioma Biomarker Discovery Laboratory

EDRN 间皮瘤生物标志物发现实验室

• 批准号: 10463892
• 负责人: HARVEY Ira PASS
• 金额: $ 22.1万
• 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 2023-01-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10463892
• 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; Malignant 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.

经常检测到与石棉相关的恶性肿瘤，恶性胸皮间皮瘤（MPM） 阶段几乎没有生存的机会。需要生物标记物来（1）确定哪些患者已经 石棉暴露（AE）（2）将AE和非MPM恶性肿瘤与MPM患者区分开，（3） 确定哪些MPM患者患有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并验证三个新型MPM血液/积液 基于标记（FBLN3，Somamer 13分类器，HMGB1同工型），并研究免疫 - 循环血细胞成分的肿瘤基因表达差异 微环境可以从其他控制队列中分层AE和MPM。所有这些在第I/II期 发现研究的AUC> 0.9。内部，新颖的基于Luminex的测定法（Soma 14 NYU MPM）由13个放慢速度速率修饰的调整器（Somamers）和一个新建的FBLN3组成 Somamer将通过相同的标本组装并在技术上进行技术验证 发现这14个分析物。等离子体和胸腔积液的诊断和预后能力 将通过健康，非AE暴露，AE，MPM和非MPM癌症进行进行，然后进行 公主玛格丽特癌症中心提供的标本中盲目验证。大学 夏威夷/雪松西奈医学中心使用202 NYU胸腔积液，将评估一个独特的技术 经过验证的，电喷雾电离液相色谱串联质谱法，用于HMGB1 它的同工型将MPM与非MPM良性和恶性积液区分开。 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 来自圣地亚哥，智利和南格拉斯哥的批准的EDRN MPM筛查计划的同伙 大学医院。最后，我们将完善并验证5个免疫 - 免疫的Budy Coat/PBMC MPM剖面 在第二阶段研究中可以将非AE个体与AE个体与MPM分开的肿瘤学基因 AUC为1.0。这些研究可能会导致3个新型平台，这些平台单独或合并可以 显着提高了早期诊断和MPM患者准确预后的机会。

项目成果

Recurrence prediction of lung adenocarcinoma using an immune gene expression and clinical data trained and validated support vector machine classifier.

• DOI: 10.21037/tlcr-23-473
• 发表时间: 2023-10-31
• 期刊: Translational lung cancer research
• 影响因子: 4

Verification of a Blood-Based Targeted Proteomics Signature for Malignant Pleural Mesothelioma.

• DOI: 10.1158/1055-9965.epi-20-0543
• 发表时间: 2020-10
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Cerciello F;Choi M;Sinicropi-Yao SL;Lomeo K;Amann JM;Felley-Bosco E;Stahel RA;Robinson BWS;Creaney J;Pass HI;Vitek O;Carbone DP
• 通讯作者: Carbone DP