Refinement and Discovery of Nuclear Matrix Protein Markers for Colorectal Cancer

结直肠癌核基质蛋白标记物的完善和发现

• 批准号: 8693603
• 负责人: KENNETH W. KINZLER
• 金额: $ 59.54万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-07 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8693603
• 关键词: Antibodies; Area; Biological Assay; Biological Markers; Blinded; Clinical; Colon Carcinoma; Colorectal Cancer; Data; Detection; Development; Early Detection Research Network; Error Sources; Evaluation; Excision; Funding; Goals; Institution; Laboratories; Liver; Malignant Neoplasms; Measurement; Metastatic Neoplasm to the Liver; Nuclear Matrix-Associated Proteins; Outcome; Phase; Population; Population Characteristics; Positioning Attribute; Proteins; Recurrence; Sampling; Series; Serum; Specimen; Testing; Time; Tissues; Validation; Work; advanced disease; assay development; base; colorectal cancer screening; novel marker; patient population; prognostic; programs; research clinical testing; research study; success; validation studies

DESCRIPTION (provided by applicant): The focus of this proposal is to continue development of a unique panel of colon cancer associated nuclear matrix proteins (NMPs), discovered and developed during our previous EDRN-sponsored, Biomarker Development Laboratory funding. NMPs offer the potential serum-based biomarkers for the early detection of colorectal cancer. This work has progressed substantially from testing of un-blinded single institution convenience samples all the way to testing of blinded, EDRN sponsored multi-institution reference sets. Markers were tested in different laboratory settings, cancer subtypes, and patient population characteristics. These data provide compelling potential for application in clinical populations. Currently two markers, CCSA-2 and CCSA-4 are poised for Phase ll-lll validation studies. We propose, with the help of established experts in assay development, to further refine those assays to position them for definitive clinical testing. In addition, we will advance NMP markers related to liver metastasis. The two major objectives 1. To OPTIMIZE AND REFINE the CCSA-2 and CCSA-4 assays and test them in a series of small scale experiments to position them for definitive evaluation within the EDRN mechanism. In specific, we aim to (a) develop robust assays for the accurate and precise measurement of CCSA-2 and CCSA-4; (b) test the assays under a variety of clinical circumstances and conditions to understand, and anticipate sources of error and potential problems in implementation that might be encountered when testing the assays on a larger scale. The goal of this first objective is to deliver two assays to validation with ample preliminary testing to maximize the potential for success in the EDRN program. 2. To develop NMP markers for liver metastasis. We have identified proteins in liver metastasis tissue specimens that are neither present in adjacent uninvolved liver nor in liver from normal donors. These proteins are prime candidates for assay development for markers of advanced disease. We propose (a) to isolate, characterize and develop antibodies for serum detection of liver metastasis proteins, (b) to evaluate these antibodies in appropriate clinical specimens for eventual delivery for EDRN validation.

描述（由申请人提供）：该提案的重点是继续开发独特的结肠癌相关核基质蛋白（NMP），该小组在我们以前的EDRN赞助的生物标志物开发实验室资金中发现和开发。 NMP提供了潜在的基于血清的生物标志物，用于早期检测结直肠癌。这项工作已从对无盲的单个机构便利样本进行的测试取得了很大的发展，到了盲人EDRN赞助的多机构参考集的测试。在不同的实验室环境，癌症亚型和患者人群特征中测试了标记。这些数据为在临床人群中应用提供了令人信服的潜力。目前，CCSA-2和CCSA-4的两个标记已准备用于LL-LLL验证研究。我们建议，在既定专家的测定开发专家的帮助下，进一步完善这些测定法，以将其定位为确定的临床测试。此外，我们将推进与肝转移有关的NMP标记。这两个主要目标1。优化和完善CCSA-2和CCSA-4分析，并在一系列的小型实验中测试它们，以将其定位为EDRN机制内的确定性评估。具体而言，我们旨在（a）开发可靠的测定法，以对CCSA-2和CCSA-4进行准确和精确的测量； （b）测试在各种临床情况和条件下要理解的测定方法，并预测在实施中可能会遇到的错误和潜在问题的来源，这可能会遇到大规模测试时会遇到的。第一个目标的目的是通过大量的初步测试进行两种测定，以最大程度地利用EDRN计划的成功。 2。开发肝转移的NMP标记。我们已经鉴定出肝转移组织标本中均不存在于相邻的未卷入肝脏中的蛋白质，也不存在于正常供体的肝脏中。这些蛋白质是用于测定晚期疾病标志的测定开发的主要候选者。我们建议（a）隔离，表征和开发用于血清检测肝转移蛋白的抗体，（b）以在适当的临床样本中评估这些抗体，以最终递送EDRN验证。