Early Detection of Breast Cancer Using Autoantibody Mar*

描述(由申请人提供)：当癌症在最早阶段被发现时，治愈的可能性非常高，因此能够检测到这些早期阶段的诊断筛查测试是至关重要的。开发癌症早期检测方法的努力传统上依赖于单一生物标记物分子。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。该项目的核心技术依赖于PI实验室的研究，在该实验室中，他开发了一种高通量方法，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大量表位，这些表位可用于识别乳腺癌的存在。这些生物标记物是在没有对其功能的先入为主概念的情况下克隆的，可以用作诊断和预后生物标记物。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。这项研究是可能的，因为有一个引人注目的标本库，由1975年至1983年底特律大都市医院的1306名患者在手术时收集的原发乳腺肿瘤组织和血清组成。此外，还收集了1992年期间参与研究的患者的随访血清。访谈跟踪一直持续到1996年，并提供了患者跟踪的数据表。超过11,000份血清在KCI设施中保持在-70℃，目前仍可用于所有初级样本。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。通过一种独特的技术组合来加强检测(携带噬菌体展示的肿瘤抗原的微阵列)，这项研究建议探索一种新的血清检测方法来检测和预测乳腺癌的结果。其原理是，我们可以克隆与患者血清中的IgG反应的表位，并利用它们来检测血清中的抗体，以区分癌症和健康人，并在标准诊断之前检测疾病。这种方法应该为无症状的妇女提供早期检测方法。

DESCRIPTION (provided by applicant): When cancer is identified at the earliest stages, the probability of cure is very high and therefore diagnostic screening tests that can detect these early stages are crucial. Efforts toward the development of early detection assays for cancers have traditionally depended on single biomarker molecules. Current technologies have been disappointing and have not resulted in diagnostic tests suitable for clinical practice. The core technology 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 breast 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 and can be used as diagnostic and prognostic biomarkers. 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. This study is possible due to a remarkable specimen bank consisting of primary breast tumor tissues and sera collected frozen at the time of surgery from 1306 patients from Detroit metropolitan hospitals from 1975 to 1983. In addition, follow-up sera were collected from participating patients through 1992. Interview follow-ups were continued until 1996 and data forms from patient follow-ups are available. Over 11,000 sera have been maintained at -70¿ C at the KCI facility and are still currently available for all primary samples. In the discovery phase, the serum antibodies have been detected by screening of large numbers of potential epitope targets on protein microarrays. By a unique combination of techniques to enhance detection (microarrays of bacteriophage-bearing displayed tumor antigens), this study proposes to investigate a novel serum assay to detect and predict outcomes for breast cancer. The principle is that we can clone epitopes reacting with IgG in patients sera and use them to detect antibodies in sera to discriminate cancer and healthy subjects and detect disease prior to standard diagnosis. Such an approach should provide an early detection assay for asymptomatic women.