The North American Mesothelioma Consortium

描述（由申请人提供）：恶性胸膜间皮瘤（MM）是一种石棉相关的恶性肿瘤，在治疗方案不可行的晚期才被发现。敏感和特异性的MM早期检测生物标志物，如SMRP和骨桥蛋白（OPN）尚待验证，而可以隔离最高进展/死亡风险患者的预后生物标志物尚不存在。北美间皮瘤联盟（NAMC）联合了在MM和预后/早期检测调查方面具有专业知识的中心的研究人员，以开发一种多方面的方法来快速发现和最终验证这些标记物。生物标志物的发现将涉及三个独立但相关的平台：基因组表达、microRNA表达和血清抗聚糖抗体（AGA）。使用计算机分析MM表达谱的初步数据揭示了一个有前途的宏基因型预后模型。对132例MM新鲜冷冻肿瘤的分析表明，单个microRNA 29c*可以将MM患者分为进展时间短和时间长组，生存时间短和生存时间长组。最后，利用一种能够测量血清AGAs超过200个聚糖的新型聚糖阵列，可以将石棉暴露的无MM患者与具有4个AGAs的MM患者（AUC 0.863）分开，并且6种自身抗体的谱可以预测MM患者的进展和生存结果。NAMC的所有三个发现平台将通过一组具有匹配血清的正常间皮和肿瘤样本的共同参考集连接起来，以便使用系统生物学方法将每个平台的有希望的标记物与其他平台相关的途径联系起来。使用这些常见的材料，NAMC将进一步发现/验证(1)元基因预后谱，(2)29c*定义MM预后的能力，(3)用于MM早期检测的其他microrna，以及(4)用于MM早期检测/预测的AGA库。除了这些研究外，还将进行血浆OPN的早期检测和验证研究。所有这些研究都可以立即进行，因为NAMC可以通过纽约大学档案馆访问来自三个不同地理区域的超过287 MM/107正常间皮新鲜冷冻组织，339 MM血清和797石棉暴露血清

DESCRIPTION (provided by applicant): Malignant Pleural Mesothelioma (MM) is an asbestos-related malignancy which is detected at an advanced stage when curative options are not feasible. Sensitive and specific early detection biomarkers for MM such as SMRP and Osteopontin (OPN) await validation, and prognostic biomarkers which can segregate patients at highest risk for progression/death do not exist. The North American Mesothelioma Consortium (NAMC) joins investigators at centers which are known for specific expertise in MM and prognostic/early detection investigations in order to develop a multifaceted approach for the rapid discovery and eventual validation of such markers. Biomarker discovery will involve three separate but related platforms: genomic expression, microRNA expression, and serum anti-glycan antibodies (AGA). Preliminary data using in silico analysis of MM expression profiling has revealed a promising metagene-type prognostic model. Analysis of 132 MM fresh frozen tumors reveals that a single microRNA, 29c*, can segregate MM patients into groups with short and long times to progression, and groups with short and long survival. Finally, using a novel glycan array capable of measuring serum AGAs to over 200 glycans, patients with asbestos exposure without MM can be segregated from those with MM (AUC 0.863) with 4 AGAs, and a profile of 6 autoantibodies can predict progression and survival outcomes for MM patients. All three of the discovery platforms for the NAMC will be linked by a common reference set of normal mesothelium and tumor samples with matching sera in order to relate promising markers from each platform to pathways involved with the other platforms using a systems biology approach. Using these common materials, the NAMC will further discover/validate (1) the metagene prognostic profile, (2) the ability of 29c* to define MM prognosis, (3) other microRNAs for early detection of MM, and (4) the repertoire of AGA for the early detection/prognostication of MM. In addition to these studies, early detection and validation studies of plasma OPN will also be performed. All of these studies can be immediately performed since the NAMC has access through the NYU Archives to over 287 MM/107 normal mesothelium fresh frozen tissues, 339 MM sera, and 797 asbestos-exposed sera from three different geographic l