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: 8287646
• 负责人: KENNETH W. KINZLER
• 金额: $ 63.25万
• 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/8287646
• 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(申请人提供)：本提案的重点是继续开发一种独特的结肠癌相关核基质蛋白(NMP)小组，该小组是在我们之前由EDRN赞助的Biomarker开发实验室资助期间发现和开发的。NMPS为早期发现结直肠癌提供了潜在的血清生物标志物。这项工作已经从对非盲单机构便利样本的测试一直到对EDRN赞助的多机构参考集的盲化测试取得了实质性进展。标记物在不同的实验室环境、癌症亚型和患者群体特征中进行测试。这些数据为临床人群提供了令人信服的应用潜力。目前，两个标记CCSA-2和CCSA-4正准备进行阶段11-11验证研究。我们建议，在成熟的化验开发专家的帮助下，进一步完善这些化验，以确定它们在临床测试中的位置。此外，我们还将研究与肝转移相关的NMP标记物。两个主要目标1.优化和改进CCSA-2和CCSA-4检测，并在一系列小规模实验中对其进行测试，以便在EDRN机制中对其进行最终评估。具体地说，我们的目标是(A)开发可靠的分析方法，以准确和精确地测量CCSA-2和CCSA-4；(B)在各种临床环境和条件下测试这些分析方法，以了解和预测在大规模测试分析方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提供两种检测方法进行验证，并进行充分的初步测试，以最大限度地提高EDRN项目的成功潜力。2.建立肝转移的NMP标志物。我们已经在肝转移组织标本中发现了既不存在于邻近未受累肝脏中的蛋白质，也不存在于正常供者的肝脏中的蛋白质。这些蛋白质是晚期疾病标志物检测开发的主要候选者。我们建议(A)分离、鉴定和开发用于血清检测肝转移蛋白的抗体，(B)在适当的临床标本中评估这些抗体，以便最终交付EDRN验证。