Auto-antibody profiling of non-small cell lung cancer

描述(由申请人提供)：在外周血中测量的肿瘤标志物可以帮助诊断和治疗非小细胞肺癌(NSCLC)，并有可能改善历史上令人沮丧的结果。产生多种肿瘤相关蛋白的循环抗体可以转化为肺癌的有价值的血液测试。初步数据支持这一假设。我们已经成功地使用噬菌体展示、生物浓缩技术和高通量荧光阵列筛选来鉴定多种已知和未知的肿瘤相关蛋白，这些蛋白可以被循环中的肿瘤相关抗体NSCLC患者特异性识别，但不能在正常人中识别。一组排列在玻璃载玻片微阵列上的噬菌体表达蛋白用于测量一组癌症患者和风险匹配对照的血清中的肿瘤相关抗体，提供了超过目前可用的循环NSCLC相关蛋白标记物的预测准确性。虽然荧光微阵列系统是识别肿瘤相关抗体识别的蛋白质的理想工具，但它还不是一个商业化的平台。这项提议的目的是将这些标记整合到分层蛋白阵列(LPA)中，这是一个为临床诊断开发的96孔ELISA型平台。LPA的高通量格式允许同时测量多个抗体标记物，这将是应用程序的核心，是对生物标记物鉴定的完美补充。LPA最初将使用一组已经确定的蛋白质进行构建和测试。我们最初的应用将是肺癌的早期检测，尽管在肺癌治疗中的多种应用是合理的。数据显示了支持进一步开发和测试这一方法的理由的可行性和概念证明。随后的第二阶段应用程序将评估在第一阶段项目中开发的应用于非小细胞肺癌筛查的检测方法。因此，这项应用的主要目标是开发一种新的非小细胞肺癌血液检测方法，可以迅速转化为临床实践。该项目的成功将预示着其他恶性疾病的类似发展。与公共卫生的相关性。肺癌的血液检测可以提高早期发现的能力和成本效益，作为降低这种疾病死亡率的可行策略。与公共卫生的相关性。肺癌的血液检测可以提高早期发现的能力和成本效益，作为降低这种疾病死亡率的可行策略。

DESCRIPTION (provided by applicant): Tumor markers, measured in peripheral blood, could assist in diagnosis and management of non-small cell lung cancer (NSCLC) and potentially improve historically dismal outcomes. Circulating antibodies, generated to a wide range of tumor-associated proteins, can be translated into a valuable blood test for lung cancer. Preliminary data supports this hypothesis. We have successfully used phage-display, biopan enrichment techniques and high throughput fluorescent array screening to identify multiple known and unknown tumor-associated proteins specifically recognized by circulating tumor-associated antibodies NSCLC patients but not in normals. A panel of phage-expressed proteins arrayed on a glass slide microarray used to measure tumor-associated antibodies in serum from a cohort of cancer patients and risk-matched controls affords predictive accuracy that exceeds that of currently available circulating NSCLC-associated protein markers. Although fluorescent microarray system is an ideal tool for identifying proteins recognized by tumor-associated antibodies, it is not a commercial-ready platform. The intent of this proposal is to incorporate these markers into a layered protein array (LPA), a 96-well ELISA type platform that has been developed for clinical diagnostics. The high-throughput format of the LPA allows measurement of multiple antibody markers simultaneously will be central to the application is a perfect complement to biomarker identification. The LPA will be initially constructed and tested using a panel of proteins that have already been identified. Our initial application will be early detection of lung cancer, although multiple applications in lung cancer management are rational. Data shows feasibility and proof of concept that supports the rationale for further development and testing of this approach. Subsequent .Phase II application will evaluate an assay developed in this Phase I project for application to screening of NSCLC. Thus, the primary goal of this application is to develop a novel blood test for NSCLC that can be rapidly translated into clinical practice. Success in this project will herald similar development in other malignant diseases. Relevance to Public Health. A blood test for lung cancer could improve the capability and cost-effectiveness of early detection as a viable strategy for reducing mortality from this disease. Relevance to Public Health. A blood test for lung cancer could improve the capability and cost-effectiveness of early detection as a viable strategy for reducing mortality from this disease.