Autoantibodies in NSCLC as Markers for Disease

描述（由申请人提供）：多种诊断和治疗策略正在被探索以改变肺癌的不良预后。在外周血中测量肿瘤标志物，可以补充不断发展的肺癌治疗临床方法。针对肿瘤相关蛋白的自身抗体可以有效地扩大肺癌血清学标志物的数量和范围，并可转化为肺癌的有价值的检测方法。我们的初步数据支持这一假设。我们使用噬菌体展示和生物技术鉴定了非小细胞肺癌（NSCLC）患者血清中针对已知和未知肿瘤相关蛋白的多种自身抗体。利用传统的免疫化学技术和新型蛋白质微阵列，我们发现癌症患者血清中存在个体肿瘤相关蛋白的自身抗体，而正常人血清中没有。由于没有单一抗体反应可能是一个全面的标志物，我们打算在这些令人兴奋的数据的基础上，通过分析各种atuantibody的血清，开发一种包容性的肺癌血液检测方法。我们已经在NSCLC患者血清中鉴定了21种由自身抗体识别的蛋白质，并使用这些蛋白质，加上通过这些技术鉴定的其他蛋白质；我们将生成一个用于抗体测量的综合蛋白质面板。荧光微阵列技术，一般应用于基因发现，是理想的这一目的。因此，本提案的主要目标是开发一种新的非小细胞肺癌血液检测方法。为了开始扩大这种方法的临床相关性，第二个目标是显示自身抗体反应与肿瘤蛋白表达的关联。数据显示可行性和概念证明，支持这一建议背后的基本原理。

DESCRIPTION (provided by applicant): A variety of diagnostic and therapeutic strategies are being explored to change poor outcomes in lung cancer. Tumor markers, measured in peripheral blood, could complement the evolving clinical approach to lung cancer management. Autoantibodies to tumor-associated proteins may effectively expand the number and range of available serologic markers for lung cancer and be translated into a valuable test for lung cancer. Our preliminary data supports this hypothesis. We used phage-display and biopan techniques to identify multiple autoantibodies to known and unknown tumor-associated proteins in the serum of non-small cell lung cancer (NSCLC) patients. Using conventional immunochemical techniques and novel protein microarray we showed that autoantibodies to individual tumor-associated proteins are found in cancer patient sera and not in normals. Because no single antibody response is likely to be a comprehensive marker, we intend to build on these exciting data and develop an inclusive blood test for lung cancer by profiling sera for a variety of atuoantibodies. We have already identified 21 proteins recognized by autoantibodies in NSCLC patient sera and using these, plus additional proteins identified with these techniques; we will generate a comprehensive a panel of proteins used for antibody measurement. Fluorescent microarray technology, applied generally to gene discovery, is ideal for this purpose. Thus the primary goal of this proposal is to develop a novel blood test for NSCLC. To begin to expand the clinical relevance of this approach, a secondary goal is to show the association of autoantibody responses to tumor protein expression. The data shows feasibility and proof of concept that supports the rationale behind this proposal.