The EDRN Mesothelioma Biomarker Discovery Laboratory

石棉相关的恶性胸膜间皮瘤(MPM)多见于晚期。 生存机会很小的阶段。需要生物标记物来(1)确定哪些患者 石棉暴露(AE)(2)区分AE和非MPM恶性肿瘤与MPM患者和(3) 确定哪些MPM患者早期复发或死亡的风险最高。EDRN 间皮瘤生物标记物发现实验室将提炼和验证三种新的MPM血液/积液 基于标记(FBLN3，SOMAmer 13分类器，HMGB1亚型)，并研究免疫- 肿瘤基因在循环血细胞成分中的表达差异 微环境可以将AE和MPM与其他对照队列区分开来。所有这些都在第一/第二阶段 发现研究已经得出了AUCS&GT；0.9。一种基于Luminex的内部新型分析方法(SOMA 14 NYU MPM)由13个慢速修饰适配子(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，这些样本用于 发现这14种分析物。血浆和胸腔积液的诊断和预后能力 将在健康的、未暴露于AE的、AE、MPM和非MPM癌症队列中进行治疗，其次是 玛格丽特公主癌症中心提供的标本的盲法验证。伊利诺伊大学 夏威夷/雪松西奈医学中心，使用202个纽约大学胸腔积液，将评估一个独特的，技术上的 HMGB1电喷雾电离液质联用分析方法的验证 及其异构体用于鉴别MPM与非MPM良、恶性积液。HMGB1 渗出结果将与SOMA 14 NYU MPM的验证结果进行比较 智利圣地亚哥和南格拉斯哥批准的EDRN MPM筛查计划的队列 大学医院。最后，我们将完善和验证我们的Buffy Coat/PBMC MPM配置文件中的5种免疫- 在第二阶段研究中，肿瘤学基因可以区分非AE患者、AE患者和MPM患者 AUCs为1.0。这些研究可能导致3个新的平台，它们单独或结合在一起可以 显著提高了MPM患者的早期诊断和准确预测的机会。

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.