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: 7983030
• 负责人: Robert H. Getzenberg
• 金额: $ 72.1万
• 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 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7983030
• 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一组独特的结肠癌相关核基质蛋白（NMP），该蛋白是在我们之前的EDRN赞助的生物标志物开发实验室资助期间发现和开发的。NMPs为结直肠癌的早期检测提供了潜在的基于血清的生物标志物。这项工作已经从揭盲的单一机构便利样本的检测一直进展到设盲的EDRN申办的多机构参考集的检测。在不同的实验室环境、癌症亚型和患者人群特征中测试标记物。这些数据为临床人群的应用提供了令人信服的潜力。目前，两种标志物CCSA-2和CCSA-4准备进行II-III期验证研究。我们建议，在检测开发方面的知名专家的帮助下，进一步完善这些检测，以使其能够进行最终的临床试验。此外，我们将推进与肝转移相关的NMP标志物。两大目标1。优化和完善CCSA-2和CCSA-4检测试剂盒，并在一系列小规模实验中对其进行测试，以将其定位为EDRN机制中的确定性评价。具体而言，我们的目标是（a）开发用于准确和精确测量CCSA-2和CCSA-4的稳健测定法;（B）在各种临床环境和条件下测试测定法，以了解并预测在更大规模测试测定法时可能遇到的误差来源和实施中的潜在问题。第一个目标的目标是通过充分的初步测试提供两种检测方法进行验证，以最大限度地提高EDRN计划的成功潜力。2.建立肝转移的NMP标志物。我们在肝转移组织标本中发现了一些蛋白质，这些蛋白质既不存在于邻近的未受累肝脏中，也不存在于正常供体的肝脏中。这些蛋白质是用于晚期疾病标志物的测定开发的主要候选物。我们建议（a）分离、表征和开发用于肝转移蛋白的血清检测的抗体，（B）在适当的临床标本中评估这些抗体，以最终交付EDRN验证。