The North American Mesothelioma Consortium

北美间皮瘤协会

• 批准号: 8137259
• 负责人: Margaret Elisabeth Huflejt
• 金额: $ 57.9万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-29 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8137259
• 关键词: American; Antibodies; Archives; Asbestos; Autoantibodies; Biological Markers; Cessation of life; Combined Modality Therapy; Computer Simulation; Data; Development; Early Diagnosis; Freezing; Genomics; Goals; Individual; Investigation; Link; Malignant Neoplasms; Malignant Pleural Mesothelioma; Measures; Mesothelioma; Mesothelium; MicroRNAs; Modeling; Molecular Profiling; Oncogenic; Outcome; Pathway interactions; Patients; Pattern; Plasma; Polysaccharides; Research Personnel; Risk; Sampling; Screening procedure; Serum; Staging; Systems Biology; Time; Tissues; Validation; base; cohort; genome-wide; health economics; high risk; improved; novel; novel strategies; osteopontin; outcome forecast; prognostic; tumor; validation studies

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

描述（由申请人提供）： 恶性胸膜间皮瘤 (MM) 是一种与石棉相关的恶性肿瘤，在治疗方案不可行时在晚期才被发现。 SMRP 和骨桥蛋白 (OPN) 等 MM 敏感且特异的早期检测生物标志物有待验证，而能够区分进展/死亡风险最高的患者的预后生物标志物尚不存在。北美间皮瘤联盟 (NAMC) 与以 MM 和预后/早期检测研究方面的特定专业知识而闻名的中心的研究人员联合起来，旨在开发一种多方面的方法来快速发现和最终验证此类标记物。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 MM 表达谱的计算机分析的初步数据揭示了一种有前途的宏基因型预后模型。对 132 个 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长的组以及生存期短和长的组。最后，使用能够测量 200 多种聚糖的血清 AGA 的新型聚糖阵列，可以将没有 MM 的石棉暴露患者与具有 4 个 AGA 的 MM (AUC 0.863) 患者区分开来，并且 6 种自身抗体的谱可以预测进展和生存结果对于MM患者。 NAMC 的所有三个发现平台将通过正常间皮和肿瘤样本与匹配血清的通用参考集连接起来，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涉及的途径联系起来。使用这些通用材料，NAMC 将进一步发现/验证 (1) 宏基因预后概况，(2) 29c* 定义 MM 预后的能力，(3) 用于早期检测 MM 的其他 microRNA，以及 (4) 库AGA 用于 MM 的早期检测/预测。除了这些研究之外，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获取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 份石棉暴露血清。