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Autoantibodies to tumor-associated antigens as diagnostic biomarkers in liver can

肿瘤相关抗原的自身抗体作为肝脏的诊断生物标志物可以

基本信息

批准号：
8704893
负责人：
JIANYING ZHANG
金额：
$ 25.38万
依托单位：
UNIVERSITY OF TEXAS EL PASO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-05 至 2016-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Antigenic changes in cancer cells can be recognized by the immune system of patients themselves and presented as immune responses to factors involved in malignant transformation. This is manifested in several ways, one of which is the appearance of circulating autoantibodies. These autoantibodies, which have been called "reporters" from the immune system, identify the antigenic changes in cellular factors involved in the transformation process. Circulating autoantibodies from cancer patients have been used to isolate the cognate tissue antigens, many of which have been shown to be cellular factors participating in known tumorigenesis pathways. These cancer-related tissue antigens have been generally called tumor-associated antigens (TAAs). In the case of liver cancer, especially hepatocellular carcinoma (HCC), antecedent liver cirrhosis and chronic hepatitis are common precursor conditions and during transition to malignancy some patients develop novel autoantibodies that were not present during the preceding chronic liver disease phase. The hypothesis is that transition to malignancy can be associated with autoantibody responses to certain cellular proteins that might have some role in tumorigenesis. It is proposed that the information that the cancer patient's immune system is conveying in the form of autoantibodies to TAAs should be utilized to a greater extent in identifying early signs of tumorigenesis. There are three specific aims in this grant application: (1) Establish more precise time lines to determine when autoantibodies to TAAs appear as early predictors of HCC in patients with antecedent chronic viral hepatitis and liver cirrhosis; (2) Identify and characterize novel TAAs in HCC using a proteome-based technology, and further validate the potential value of the identified TAAs as cancer biomarkers; (3) Establish rigorous criteria for designation of an autoantibody to a TAA as a cancer biomarker, examine candidate TAAs for sensitivity and specificity of anti-TAA antibody response, and further develop customized TAA arrays that can be used to enhance anti-TAA antibody detection in HCC.

描述(申请人提供)：癌细胞中的抗原性变化可以被患者自身的免疫系统识别，并表现为对涉及恶性转化的因素的免疫反应。这表现在几个方面，其中之一就是循环中的自身抗体的出现。这些自身抗体被称为来自免疫系统的“记者”，它们识别转化过程中涉及的细胞因子的抗原性变化。来自癌症患者的循环自身抗体已被用于分离同源组织抗原，其中许多已被证明是参与已知肿瘤发生途径的细胞因子。这些与癌症相关的组织抗原通常被称为肿瘤相关抗原(TAA)。对于肝癌，特别是肝细胞癌，先发的肝硬变和慢性肝炎是常见的先兆条件，在向恶性肿瘤的转变过程中，一些患者产生了在前一慢性肝病阶段不存在的新的自身抗体。该假说认为，向恶性肿瘤的转变可能与对某些细胞蛋白的自身抗体反应有关，这种抗体可能在肿瘤发生中起到一定作用。有人建议，癌症患者的免疫系统以抗TAA自身抗体的形式传递的信息应该在更大程度上被用于识别肿瘤发生的早期迹象。这项赠款申请有三个具体目标：(1)建立更精确的时间线，以确定TAA自身抗体何时出现为既往慢性病毒性肝炎和肝硬变患者肝细胞癌的早期预测因素；(2)利用基于蛋白质组的技术鉴定和表征新的肝细胞癌患者的TAA，并进一步验证已确定的TAA作为癌症生物标志物的潜在价值；(3)为将TAA自身抗体指定为癌症生物标志物建立严格的标准，检查候选TAA抗TAA抗体反应的敏感性和特异性，并进一步开发可用于增强肝细胞癌抗TAA抗体检测的定制TAA阵列。