Autoantibodies in NSCLC as Markers for Disease

描述（由申请人提供）：正在探索各种诊断和治疗策略，以改变肺癌的不良结局。在外周血中测量的肿瘤标志物可以补充肺癌管理的不断发展的临床方法。肿瘤相关蛋白自身抗体可有效地扩大肺癌血清学标志物的数量和范围，并转化为有价值的肺癌检测。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淘选技术来鉴定非小细胞肺癌（NSCLC）患者血清中已知和未知肿瘤相关蛋白的多种自身抗体。使用传统的免疫化学技术和新的蛋白质微阵列，我们发现，个别肿瘤相关蛋白的自身抗体被发现在癌症患者的血清中，而不是在正常人。因为没有单一的抗体反应可能是一个全面的标志物，我们打算建立在这些令人兴奋的数据，并开发一个包容性的肺癌血液检测，通过分析血清中的各种抗体。我们已经鉴定了NSCLC患者血清中自身抗体识别的21种蛋白质，并使用这些蛋白质，加上用这些技术鉴定的其他蛋白质;我们将产生一个全面的用于抗体测量的蛋白质组。荧光微阵列技术，一般应用于基因发现，是理想的，为此目的。因此，该提案的主要目标是开发一种新的NSCLC血液检测方法。为了开始扩展这种方法的临床相关性，第二个目标是显示自身抗体应答与肿瘤蛋白表达的关联。数据显示了可行性和概念证明，支持这一建议背后的理由。

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.