Development and Validation of a Panel of Breast Cancer for the Early Diagnosis of

用于早期诊断的乳腺癌组的开发和验证

• 批准号: 7527746
• 负责人: FELIX Rodolfo FERNANDEZ-MADRID
• 金额: $ 56.72万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7527746
• 关键词: Antibodies; Antigens; Autoantibodies; Autoantigens; Bacteriophages; Behavior; Benign; Biological Markers; Biopsy; Blood Tests; Breast; Clinical; Clinical Trials; Cloning; Code; Collection; Complement; Data; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Health Maintenance Organizations; Health system; Human; Invasive; Investigation; Malignant Neoplasms; Mammography; Meta-Analysis; Methods; Noninfiltrating Intraductal Carcinoma; Outcome; Outcome Measure; Participant; Patients; Performance; Process; Proteins; Public Health; Recombinants; Reporting; Sampling; Screening procedure; Sensitivity and Specificity; Serum; Staging; Testing; Tissue Procurements; To autoantigen; Validation; Woman; Women' s Group; abstracting; base; breast cancer diagnosis; cDNA Library; cancer prevention; cancer risk; case control; diagnostic accuracy; ductal breast carcinoma; follow-up; improved; instrument; malignant breast neoplasm; member; mortality; novel diagnostics; response; tool; tumor

DESCRIPTION (provided by applicant): Development and validation of a panel of breast cancer autoantigens for the early diagnosis of breast cancer Abstract Detection of the early stages of breast cancer is one of the pillars of successful therapy and the identification of cancer risk is paramount in cancer prevention. Meta-analyses of data from clinical trials support the conclusion that annual screening mammography reduces breast cancer mortality. Although there is support for its use as a screening tool for breast cancer, mammography has known limitations, mainly false negative and false positive results. On this basis, we propose a new method which will complement and improve the accuracy of screening mammography to detect breast cancer early and accurately. Many studies have shown that autoantibodies appear in cancer sera before the disease becomes clinically evident, suggesting that they have the potential of detecting early disease, i.e., when the treatment has the best chance to influence tumor behavior and ideally to achieve a cure. In response to the need of accurate biomarkers predictive of early diagnosis of breast cancer, we developed an autoantigen panel based on autoantibody recognition of phage-encoded human antigens for the diagnosis of breast cancer. The primary objective of this proposal is to improve the accuracy of this diagnostic panel. The accuracy of the panel will be improved by identifying a larger pool of breast cancer-associated autoantigens with potential diagnostic value. This will be accomplished by using sera from women with ductal carcinoma in situ (DCIS) of the breast for cloning the new antigens, and by selecting cloning sera containing antibodies not previously used for immunoscreening. The performance of the expanded antigen panel will be tested by probing the microarray with an existing collection of sera from women with biopsy-proven diagnosis of DCIS and, infiltrating ductal carcinoma (IDC) of the breast and complete follow up, including mammography findings and outcome measures obtained from the Tissue Procurement Facility at the Henry Ford Health System (HFHS). Control sera will be obtained prospectively from women undergoing mammography screening at HFHS with final assessment of BI-RADS 4 and benign diagnosis at breast biopsy. We propose to validate the performance of the expanded panel constructed with phage inserts in a racially diverse group of women with mammography BI-RADS 4 final assessment, who are members of a large health maintenance organization and regular participants in mammography screening. Finally, we will develop a specific ELISA using the identified phage antigens as substrates which will be reacted with the same case and control sera used to validate the microarray. The outcome of this project will be the development of a new diagnostic test based on serum reactivity to an autoantigen panel, which will prove to be an accurate, relatively inexpensive, accessible, rapid and easy test to perform, which may effectively improve the accuracy of screening mammography for the early diagnosis of breast cancer with potential for the identification of breast cancer risk. PUBLIC HEALTH RELEVANCE: This project is based on a reported case-control investigation of a phage-coded autoantigen panel that could distinguish breast cancer sera from normal controls without cancer and appeared to be a promising test for the early diagnosis of breast cancer. Here we propose to improve the accuracy of the reported panel by concentrating our efforts on DCIS of the breast, the first clinically recognizable form of breast cancer, by expanding the diagnostic panel through the identification of new breast cancer- associated phage-coded autoantigens and to validate this array in an independent group of women from the Henry Ford Health System with BI-RADS 4 final assessment at mammography. A portable ELISA constructed with the antigens identified will be probed with the case and control sera used to externally validate the panel to assess the potential value of this platform in a clinical setting. The outcome of this project will be the development of a new diagnostic instrument, based on serum reactivity to an autoantigen panel constructed with phage-coded antigens which may prove to be an accurate, relatively inexpensive, accessible, rapid and easy to administer blood test for the early diagnosis of breast cancer. We propose that this test used in conjunction with mammography has the potential to complement and increase the accuracy of the screening process.

描述（由申请人提供）：乳腺癌早期诊断的乳腺癌自身抗原的开发和验证抽象发现乳腺癌的早期阶段是成功治疗的支柱之一，癌症风险的鉴定对于预防癌症是至关重要的。来自临床试验的数据的荟萃分析支持这样的结论，即每年乳腺检查降低乳腺癌的死亡率。尽管它支持其用作乳腺癌的筛查工具，但乳房X线摄影具有已知的局限性，主要是假阴性和假阳性结果。在此基础上，我们提出了一种新方法，该方法将补充并提高筛查乳房X线摄影的准确性，以尽早，准确地检测乳腺癌。许多研究表明，在该疾病在临床上明显之前，自身抗体出现在癌症血清中，这表明它们有可能检测早期疾病，即治疗有最好的机会影响肿瘤行为并理想地治愈。为了响应需要预测乳腺癌早期诊断的准确生物标志物，我们基于自身抗体识别噬菌体编码的人类抗原的自身抗原面板来诊断乳腺癌。该建议的主要目的是提高该诊断面板的准确性。通过鉴定具有潜在诊断值的较大乳腺癌相关的自身抗原，将提高面板的准确性。这将通过使用乳房原位导管癌女性的血清来克隆新抗原，并选择含有以前未用于免疫镜的抗体的克隆血清。扩展的抗原面板的性能将通过探测微阵列的现有血清，这些血清来自对DCI的活检诊断为诊断为DCIS的妇女以及乳房浸润的导管癌（IDC）的完整后续跟进，并进行了完整的后续跟进，包括乳房摄影发现和结果测量结果，包括从组织采购设施中获得的Henry System（Hef for Henry for for Henry for for Henry ford for the Henry ford for ded Health ford for ded hef for the Henry ford ford ford ford ford ford ford ford ford ford ford ford ford ford ford ford ford ford ford ford ford ford。对照血清将从在HFHS进行乳房X线摄影筛查的女性前瞻性获得，并最终评估BI-RADS 4和乳房活检时的良性诊断。我们建议验证在种族多样化的乳房X线摄影Bi-Rads 4 Final评估的种族多样化的女性中，噬菌体插入材料的扩展面板的性能，这些妇女是大型健康维护组织的成员和乳房X线摄影筛查的常规参与者。最后，我们将使用鉴定出的噬菌体抗原作为底物开发特定的ELISA，该底物将与相同的情况和用于验证微阵列的控制血清反应。该项目的结果将是基于对自身抗原面板的血清反应性的新诊断测试的开发，该测试将被证明是一种准确，相对廉价，易于访问，快速，快速和易于执行的测试，这可能有效地提高了筛查乳腺造影的准确性，从而可以对乳腺癌的早期诊断具有乳腺癌风险的诊断潜力。公共卫生相关性：该项目基于据报道对噬菌体编码自动抗原面板的病例对照研究，该研究可以将乳腺癌血清与没有癌症的正常对照区分开，并且似乎是对乳腺癌早期诊断的有希望的测试。在这里，我们建议通过将我们的精力集中在乳房DCI上，这是第一种临床上可识别的乳腺癌形式，通过通过鉴定新的乳腺癌与Henry Ford Health System a Henry Ford Health System在Bi-Rads的独立女性中验证这一阵列的乳腺癌的乳腺癌的第一种临床识别形式，这是诊断面板的准确性。用抗原构建的便携式ELISA将与案例进行探测，并使用用于外部验证面板的控制血清，以评估该平台在临床环境中的潜在值。该项目的结果将是基于对噬菌体编码抗原构建的自身抗原面板的血清反应性的开发，该抗原可能被证明是一种准确，相对廉价，易于获得，快速且易于对早期乳腺癌诊断的血液测试。我们建议与乳房X线摄影结合使用的该测试有可能补充和提高筛查过程的准确性。