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

描述（申请人提供）：癌细胞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中的抗原变化。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）。在肝癌的情况下，特别是肝细胞癌（HCC），先前的肝硬化和慢性肝炎是常见的前驱病症，并且在向恶性肿瘤转变期间，一些患者产生在先前的慢性肝病阶段期间不存在的新型自身抗体。该假说认为，向恶性转化可能与对某些细胞蛋白质的自身抗体反应有关，这些蛋白质可能在肿瘤发生中起一定作用。建议癌症患者的免疫系统以TAA自身抗体的形式传递的信息应在更大程度上用于识别肿瘤发生的早期迹象。该基金申请有三个具体目标：（1）建立更精确的时间线，以确定TAA自身抗体何时出现作为既往慢性病毒性肝炎和肝硬化患者HCC的早期预测因子;（2）使用基于蛋白质组的技术鉴定和表征HCC中的新型TAA，并进一步验证所鉴定的TAA作为癌症生物标志物的潜在价值;（3）建立将TAA自身抗体指定为癌症生物标志物的严格标准，检查候选TAA的抗TAA抗体应答的灵敏度和特异性，并进一步开发可用于增强HCC中抗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.