American/Australian 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。预测石棉暴露、MM高风险个体将发展MM的敏感和特异性生物标志物不存在。通过联合美国和澳大利亚的研究人员的努力，这些研究人员以其在实验研究和MM新方案方面的专业知识而闻名，将采取多方面的方法来快速发现和最终验证早期间皮细胞癌变的标志物。该联盟将拥有世界上最大的用于MPM生物标志物发现的试剂集合，包括存档和未来收集的标本。在已经建立的工业合作的基础上，两个中心将首先通过改进潜在的间皮生物标志物SMRP（间皮素/巨核细胞增强因子相关蛋白的可溶性成员）建立联系。初步数据显示，与其他癌症和石棉暴露个体相比，MPM患者的血清和胸腔积液有选择性上调。石棉暴露个体SMRP正常范围的标准将使用现有的bbb2000澳大利亚患者血清档案建立，ELISA的阳性/阴性预测值将使用现有的和未来收集的MM患者血清来确定。美国和澳大利亚的研究中心也将使用Affymetrix表达阵列平台，通过比较非癌性间皮瘤和早期间皮瘤肿瘤来定义新的可溶性生物标志物。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、MMP-3和软骨连接蛋白1可能是检测MPM的有希望的标志物。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两个地点进行。

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.