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

描述（由申请人提供）：癌细胞中的抗原变化可以被患者自身免疫系统识别，并表现为对恶性转化相关因素的免疫反应。这表现在几个方面，其中之一是循环自身抗体的出现。这些自身抗体，被称为免疫系统的“报告者”，识别参与转化过程的细胞因子的抗原变化。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，其中许多抗原已被证明是参与已知肿瘤发生途径的细胞因子。这些癌症相关组织抗原通常被称为肿瘤相关抗原（TAAs）。在肝癌，特别是肝细胞癌（HCC）的情况下，既往肝硬化和慢性肝炎是常见的前驱疾病，在向恶性肿瘤过渡期间，一些患者产生在先前的慢性肝病阶段不存在的新的自身抗体。假设是，向恶性肿瘤的转变可能与某些细胞蛋白的自身抗体反应有关，这些细胞蛋白可能在肿瘤发生中起一定作用。我们建议，癌症患者的免疫系统以TAAs自身抗体的形式传递的信息应该在更大程度上用于识别肿瘤发生的早期迹象。该资助申请有三个具体目的：(1)建立更精确的时间线，以确定TAAs自身抗体何时出现为慢性病毒性肝炎和肝硬化患者HCC的早期预测因子；(2)使用基于蛋白质组学的技术鉴定和表征HCC中的新型TAAs，并进一步验证鉴定的TAAs作为癌症生物标志物的潜在价值；(3)建立严格的TAA自身抗体作为癌症生物标志物的指定标准，检测候选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癌抗TAA抗体检测的定制TAA阵列。

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.