Identifying Tumor-Associated Antigens for Detection of Hepatocellular Carcinoma

肝癌，尤其是肝细胞癌（HCC），影响美国的西班牙裔人口。 是白色人口的两倍。这一统计数据从早期就已经很明显了。 70年代，并继续在整个美国不同的西班牙裔人口举行。大多数 患有HCC的人会在发现后1年内死亡。这种高病死率可能部分是 原因是缺乏早期诊断方法。癌症血清含有抗体 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，不仅涉及遗传， 赋予生长优势的变化，以及破坏生长调节的因素， 分化有可能确定其中一些因素并对其功能进行评估 在肿瘤发生过程中产生的自身抗体的帮助下。多因素和多步骤的性质 人类癌症的分子发病机理必须在设计和 对研究进行解释，以确定对癌症早期检测有用的标志物。这 应用集中在三个具体目标：（1）鉴定和表征TAA作为HCC中的标志物 使用SEREX（重组cDNA表达文库的血清学分析）的两种方法 和蛋白质组学分析;（2）研究鉴定的TAA在HCC中的表达频率， 免疫组化法检测癌组织中抗体的表达，并探讨癌血清中抗体与表达的关系 癌组织标本中相应的靶抗原，以进一步验证 TAA作为HCC标志物的可能性;（3）确定多个TAA的微型阵列是否 增强抗体检测，是一种有用的非侵入性方法，用于HCC的免疫诊断。的 基本原理是，在HCC患者的血清中， 从慢性肝病到HCC，在此进展过程中出现的新型自身抗体可能是 报告与肿瘤发生相关的事件，因此自身抗体可用作 SEREX中的探针和基于蛋白质组的方法，以识别可能涉及的抗原 恶性转化 摘要：大多数肝细胞癌（HCC）患者将在1年内死亡。 侦测这种高病死率的部分原因是缺乏诊断方法， 早期检测在这项研究中，我们将确定是否有一个微型阵列的多个肿瘤相关的， 抗原将增强抗体检测，并进一步开发一种有用的非侵入性方法， 人类HCC的早期检测

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