American/Australian Mesothelioma Consortium

描述(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，在治疗方案不可行的晚期被发现。不存在预测暴露于石棉的多发性骨髓瘤高危个体患多发性骨髓瘤的敏感和特异的生物标志物。通过结合美国和澳大利亚中心的研究人员的努力，这些中心以其在工作台调查方面的专业知识和MM的新方案而闻名，将采取一种多方面的方法来快速发现和最终验证早期间皮癌发生的标志物。该联盟将拥有世界上最大的MPM生物标记物发现试剂集合，无论是存档标本还是预期收集的标本。这些中心最初将通过改进潜在的间皮细胞生物标记物SMRP(间皮细胞/巨核细胞增强因子相关蛋白的可溶性成员)来建立联系，建立在已经建立的行业合作的基础上。初步数据显示，与其他癌症和石棉接触者相比，MPM患者血清和胸腔积液中的选择性上调。将使用现有的&gt；2000患者澳大利亚血清档案建立暴露于石棉的个人的SMRP正常范围的标准，并将使用现有的和预期收集的多发性骨髓瘤患者的血清来确定ELISA法的阳性/阴性预测值。美国和澳大利亚的网站还将使用Affymetrix Expression阵列平台，通过比较非癌症间皮细胞与从研究人员档案中切除的早期间皮瘤肿瘤来定义新的可溶生物标记物。结合基因表达数据和分泌蛋白通路分析的初步数据表明，骨桥蛋白、基质金属蛋白酶-3和软骨连接蛋白1可能是检测MPM的有前途的标记物。这些标记物的进一步验证以及有前景的新型生物标记物试剂的开发将在美国和澳大利亚进行。

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 biomarkers which predict that an asbestos-exposed, high-risk-for-MM individual will develop MM do not exist. By combining the efforts of investigators in the United States and Australia at centers which are known for their expertise in bench work investigations and novel protocols for MM, a multifaceted approach for the rapid discovery and eventual validation of markers of early mesothelial carcinogenesis will be undertaken. This consortium will have the largest collection of reagents for biomarker discovery in MPM in the world, both as archived and prospectively collected specimens. The centers will be linked initially through the refinement of the potential mesothelial biomarker SMRP (soluble members of the mesothelin/Megakaryocyte Potentiating Factor related protein) building on already established industrial collaborations. Preliminary data reveals selective upregulation in sera and pleural effusions of MPM patients compared to other cancers and asbestos exposed individuals. Standards for the normal range of SMRP in asbestos exposed individuals will be established using an already existing >2000 patient Australian serum archive, and the positive/negative predictive value of the ELISA will be determined using existing and prospectively collected sera from MM patients. Both the US and Australian sites will also use the Affymetrix Expression Array Platform to define new soluble biomarkers by comparing non-cancerous mesothelium to early stage, resected mesothelioma tumors from the investigators archives. Preliminary data combining gene expression data with pathway analyses for secreted proteins suggests that osteopontin, MMP-3, and Cartilage Link Protein 1 could be promising markers for the detection of MPM. Further validation of these markers as well as the development of reagents for promising novel biomarkers will be performed at both the US and the Australian sites.