Identifying Tumor-Associated Antigens for Detection of Hepatocellular Carcinoma

鉴定肿瘤相关抗原以检测肝细胞癌

• 批准号: 7858091
• 负责人: JIANYING ZHANG
• 金额: $ 12.29万
• 依托单位: UNIVERSITY OF TEXAS EL PASO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7858091
• 关键词: Accounting; Affect; American; Antibodies; Antigen Targeting; Antigens; Autoantibodies; Autologous; Biological Markers; Case Fatality Rates; Chronic; Chronic Hepatitis; Clinical Data; Data Collection; Detection; Development; Diagnosis; Diagnostic Procedure; Differentiation and Growth; Early Diagnosis; Enhancing Antibodies; Event; Expression Library; Frequencies; Goals; Growth; Hispanics; Human; Immunohistochemistry; Immunological Diagnosis; Individual; Liver Cirrhosis; Liver diseases; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of liver; Molecular; Mutation; Nature; Pathogenesis; Patients; Population; Predictive Value; Primary carcinoma of the liver cells; Process; Proteome; Proteomics; Recombinants; Regulation; Reporter; Screening for cancer; Sensitivity and Specificity; Serological; Serum; Specimen; System; Technology; Texas; Tissue Sample; Tissues; Tumor Antigens; United States; Universities; Validation; abstracting; base; cDNA Expression; cancer type; design; novel; programs; statistics; tumorigenesis

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

肝癌，尤其是肝细胞癌（HCC），影响了联合的西班牙裔人口 州的速度是白人人口的两倍。自早期以来，这种统计数据就已经很明显了 70年代，并继续遍及整个美国西班牙裔人口。大多数 HCC患者在发现后的1年内将死亡。这种高病态率可以部分 归因于缺乏允许早期检测的诊断方法。癌症血清含有抗体 它与独特的自体细胞抗原反应称为肿瘤相关抗原 （taas）。癌症长期以来被认为是一个多步骤过程，不仅涉及遗传 变化赋予增长优势，以及破坏增长和调节的因素 分化。这些因素中的某些因素可能可以识别出来并评估其功能 借助于肿瘤发生期间产生的自身抗体。多因素和多步骤的性质 在设计和 对研究的解释，以鉴定标记物，这些标志物可用于早期检测癌症。这 应用集中于三个特定目标：（1）识别和将TAA作为HCC中的TAA作为标记 使用两种方法（重组cDNA表达文库的血清学分析） 和蛋白质组学分析； （2）研究使用HCC中鉴定出的TAA的表达频率 免疫组织化学并探索癌症血清中抗体与表达之间的关系 癌组织标本中相应的靶向抗原，以进一步验证电势 在HCC中将TAA作为标记的可能性； （3）确定多个TAA的迷你阵列是否会 增强抗体检测，是对HCC免疫诊断的有用的无创方法。这 理由是，在来自HCC患者的血清中，他们在进展过程中显示自身抗体变化 慢性肝疾病到HCC，在此过程中出现的新型自身抗体可能是 与肿瘤发生有关的事件的记者，因此可以将自身抗体用作 基于Serex和蛋白质组方法中的探针，以鉴定潜在涉及的抗原 在恶性转化中。 简短摘要：大多数患有肝细胞癌（HCC）的人将在其1年内死亡 检测。这种高病态率的率可以部分归因于缺乏诊断方法 早期检测。在这项研究中，我们将确定是否有多个肿瘤相关的微型阵列 抗原将增强抗体检测，并进一步开发出一种有用的非侵入性方法 早期发现人类HCC