Markers for the Early Detection of Ovarian Cancer

描述(由申请人提供) 目前的技术一直令人失望，还没有产生适合临床实践的诊断测试。该项目的目标是检测患者对卵巢肿瘤中表达的蛋白质产生的抗体，并将其用作诊断生物标记物。这个项目的核心基于PI的实验室的研究，在该实验室中，他开发了一种高通量方法来识别大量表位，这些表位可以通过检测测试对象血清中是否存在针对肿瘤蛋白的自身抗体来识别卵巢癌的存在。这些生物标记物是在没有对其功能的先入为主的概念的情况下克隆的。该方法的基本特征是承认任何特定类型癌症的异质性，摆脱对任何单一标记物的疾病检测的依赖，并使用专门的生物信息学技术来解释结果。该概念使用多个标记物的模式识别作为诊断，而不是任何单一标记物。在发现阶段，通过在蛋白质芯片上筛选大量潜在的表位靶点来检测血清抗体。我们开发了一种有效的早期检测卵巢癌(OVCA)的筛选试验，该方法使用cDNAT7噬菌体展示文库来分离编码与卵巢癌患者血清中特异性抗体反应的表位的cDNA。这些表位的分离是通过我们的差异生物扫描技术实现的，该技术使用从健康对照组和卵巢癌患者收集的人血清。我们从OVCA患者血清中存在的与免疫球蛋白-G分子(IGG)结合的基因的cDNA中筛选出噬菌体展示肿瘤细胞库，而OVCA患者血清中的免疫球蛋白-G分子不与正常血清中的IGG结合。与大量这些表位的血清反应是在蛋白质微阵列上高度平行的分析中检测到的。其原理是克隆与患者血清中的IgG反应的表位，并用它们来检测血清中的抗体，以区分癌症和健康人，以及我们是否可以在标准诊断之前发现疾病。

DESCRIPTION (provided by applicant) Current technologies have been disappointing and have not resulted in diagnostic test suitable for clinical practice. The goal of this project is to detect antibodies that are produced by patients in reaction to proteins expressed in their ovarian tumors and use them as diagnostic biomarkers. The core of this project rests on research from the PI's lab in which he has developed a high throughput method to identify large numbers of epitopes that can be used to identify the presence of ovarian cancer by detecting the presence of auto-antibodies to tumor proteins in the serum of the test subject. These biomarkers are cloned without a preconceived notion of their function. The essential features of the approach are acknowledging the heterogeneous nature of any specific kind of cancer, departing from the reliance on any single marker for disease detection, and using specialized bioinformatics techniques to interpret the results. The concept employs pattern recognition of multiple markers as a diagnostic rather than any single marker. In the discovery phase, the serum antibodies have been detected by screening of large numbers of potential epitope targets on protein microarrays. We developed an effective screening test for early detection of ovarian cancer (OVCA) using cDNA T7 phage display libraries to isolate cDNAs coding for epitopes reacting with antibodies present specifically in the sera of patients with ovarian cancer. The isolation of these epitopes is achievable by our differential biopanning technology using human sera collected both from healthy controls and patients having ovarian cancer. We screen phage display tumor cell libraries from OVCA fro cDNAs of genes that bind immunoglobulin-G molecules (IgGs) present in OVCA patients' sera and do not bind to IgGs from normal sera. The serum reaction with large numbers of these epitopes is be detected in a highly parallel assay on protein microarrays. The principle is that we clone epitopes reacting with IgG in patients sera and use them to detect antibodies in sera to discriminate cancer and healthy subjects and whether we can detect disease prior to standard diagnosis.