Markers for the Early Detection of Ovarian Cancer

描述（由申请人提供） 目前的技术是令人失望的，并没有导致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志物。 该项目的核心在于PI实验室的研究，他开发了一种高通量方法来鉴定大量表位，这些表位可用于通过检测受试者血清中肿瘤蛋白自身抗体的存在来鉴定卵巢癌的存在。 这些生物标志物的克隆没有对其功能的先入为主的概念。 该方法的基本特征是承认任何特定类型癌症的异质性，脱离对任何单一疾病检测标记的依赖，并使用专门的生物信息学技术来解释结果。 该概念采用多个标记的模式识别作为诊断，而不是任何单一标记。 在发现阶段，通过在蛋白质微阵列上筛选大量潜在的表位靶标来检测血清抗体。 我们开发了一种有效的筛选试验，用于卵巢癌（OVCA）的早期检测，使用cDNA T7噬菌体展示文库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淘选技术，使用从健康对照和卵巢癌患者收集的人血清来实现的。 我们从OVCA的噬菌体展示肿瘤细胞文库中筛选结合OVCA患者血清中存在的免疫球蛋白-G分子（IgG）而不结合正常血清中IgG的基因的cDNA。 在蛋白质微阵列上的高度平行测定中检测与大量这些表位的血清反应。 其原理是我们克隆与患者血清中IgG反应的表位，并使用它们来检测血清中的抗体，以区分癌症和健康受试者，以及我们是否可以在标准诊断之前检测疾病。

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.