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管理非小细胞肺癌（NSCLC），并可能改善历史上令人沮丧的结局。循环抗体，产生广泛的肿瘤相关蛋白，可以转化为一个有价值的血液检测肺癌。初步数据支持这一假设。我们已经成功地使用噬菌体展示，生物富集技术和高通量荧光阵列筛选，以确定多种已知和未知的肿瘤相关蛋白特异性识别的循环肿瘤相关抗体非小细胞肺癌患者，而不是在正常人。一组排列在载玻片微阵列上的噬菌体表达的蛋白质用于测量来自癌症患者和风险匹配对照组的血清中的肿瘤相关抗体，其提供的预测准确性超过目前可用的循环NSCLC相关蛋白质标记物。尽管荧光微阵列系统是鉴定肿瘤相关抗体识别的蛋白质的理想工具，但它不是一个商业化的平台。本提案的目的是将这些标记物纳入分层蛋白阵列（LPA），这是一种已开发用于临床诊断的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，这将是该应用的核心，是对生物标记物鉴定的完美补充。LPA最初将使用一组已经鉴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，尽管在肺癌管理中的多种应用是合理的。数据显示了可行性和概念证明，支持进一步开发和测试这种方法的理由。随后，II期申请将评估在I期项目中开发的用于筛查NSCLC的检测方法。因此，本申请的主要目标是开发一种可快速转化为临床实践的新型NSCLC血液检测方法。该项目的成功将预示着其他恶性疾病的类似发展。与公共卫生相关。肺癌的血液检测可以提高早期检测的能力和成本效益，作为降低这种疾病死亡率的可行策略。与公共卫生相关。肺癌的血液检测可以提高早期检测的能力和成本效益，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.