Identifying Tumor-Associated Antigens for Detection of Hepatocellular Carcinoma

肝癌，特别是肝细胞癌，影响美国的西班牙裔人口 美国各州的人口比例是白人人口的两倍。自早期以来，这种统计数据一直很明显 70年代的S，并继续保持在整个多元化的美国拉美裔人口。大多数人 肝细胞癌患者将在被发现后一年内死亡。这种高病死率在一定程度上可能是 归因于缺乏能够及早发现的诊断方法。癌症血清中含有抗体 它们与一组独特的称为肿瘤相关抗原的自体细胞抗原发生反应 (TAAS)。长期以来，癌症被认为是一个多步骤的过程，不仅涉及基因 赋予增长优势的变化，但也有扰乱增长和 差异化。这些因素中的一些可以被识别并评估它们的功能 借助于肿瘤形成过程中产生的自身抗体。多因素、多步骤的性质 在设计和设计中都必须考虑到人类癌症的分子发病机制 对有助于癌症早期发现的标记物的研究进行解释。这 应用主要集中在三个具体目标上：(1)识别和表征作为肝癌标志物的TAA 使用SEREX的两种方法(重组基因表达文库的血清学分析) 和蛋白质组学分析；(2)研究已鉴定的TAA在肝细胞癌中的表达频率 免疫组织化学，并探讨癌血清中抗体与表达的关系 肿瘤组织标本中相应的靶向抗原以进一步验证其潜力 TAA作为肝癌标志物的可能性；(3)确定多个TAA的微阵列是否会 加强抗体检测，是一种有用的非侵入性肝癌免疫诊断方法。这个 其基本原理是，在肝细胞癌患者的血清中，在从 从慢性肝病到肝细胞癌，在这一过程中出现的新的自身抗体很可能是 与肿瘤发生有关的事件的记者，因此自身抗体可用作 以Serex和蛋白质组为基础的方法中的探针，以识别可能涉及的抗原 在恶变过程中。 摘要：大多数肝细胞癌患者将在发病后1年内死亡。 侦测。如此高的病死率可以部分归因于缺乏诊断方法 及早发现。在这项研究中，我们将确定一个与多个肿瘤相关的微阵列 抗原将增强抗体检测，并进一步发展一种有用的非侵入性方法，用于 人肝细胞癌的早期发现

Liver cancer, especially hepatocellular carcinoma (HCC), affects the Hispanic population of the United States at a rate double that of the white population. This statistics has been evident since the early 70's, and continues to hold throughout the diverse American Hispanic population. The majority of people with HCC will die within 1 year of its detection. This high case-fatality rate can in part be attributed to lack of diagnostic methods that allow early detection. Cancer sera contain antibodies which react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). Cancer has long been recognized as a multi-step process which involves not only genetic changes conferring growth advantage but also factors which disrupt regulation of growth and differentiation. It is possible that some of these factors could be identified and their functions evaluated with the aid of autoantibodies arising during tumorigenesis. The multi-factorial and multi-step nature in the molecular pathogenesis of human cancers must be taken into account in both the design and interpretation of studies to identify markers which will be useful for early detection of cancer. This application is focused on three specific aims: (1) to identify and characterize TAAs as markers in HCC using both approaches of SEREX (Serological Analysis of Recombinant cDNA Expression Libraries) and proteomic analysis; (2) to investigate the frequency of expression of identified TAAs in HCC using immunohistochemistry, and explore the relationship between antibodies in cancer sera and expression of corresponding targeted antigens in cancer tissue specimens to further validate the potential possibility of TAAs as markers in HCC; (3) to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful non-invasive approach for immunodiagnosis of HCC. The rationale is that in sera from HCC patients who show autoantibody changes during progression from chronic liver diseases to HCC, novel autoantibodies appearing during this progression will likely be reporters of events associated with tumorigenesis, and therefore autoantibodies can be used as probes in SEREX and proteome-based approaches to identify antigens which are potentially involved in malignant transformation. Short abstract: The majority of people with hepatocellular carcinoma (HCC) will die within 1 year of its detection. This high case-fatality rate can in part be attributed to lack of diagnostic methods that allow early detection. In this study, we will determine whether a mini-array of multiple tumor-associated antigens would enhance antibody detection and further develop a useful non-invasive approach for the early detection of human HCC