Liver cancer, especially hepatocellular carcinoma (HCC), affects the Hispanic population of the UnitedStates at a rate double that of the white population. This statistics has been evident since the early70's, and continues to hold throughout the diverse American Hispanic population. The majority ofpeople with HCC will die within 1 year of its detection. This high case-fatality rate can in part beattributed to lack of diagnostic methods that allow early detection. Cancer sera contain antibodieswhich 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 geneticchanges conferring growth advantage but also factors which disrupt regulation of growth anddifferentiation. It is possible that some of these factors could be identified and their functions evaluatedwith the aid of autoantibodies arising during tumorigenesis. The multi-factorial and multi-step nature inthe molecular pathogenesis of human cancers must be taken into account in both the design andinterpretation of studies to identify markers which will be useful for early detection of cancer. Thisapplication is focused on three specific aims: (1) to identify and characterize TAAs as markers in HCCusing 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 usingimmunohistochemistry, and explore the relationship between antibodies in cancer sera and expressionof corresponding targeted antigens in cancer tissue specimens to further validate the potentialpossibility of TAAs as markers in HCC; (3) to determine whether a mini-array of multiple TAAs wouldenhance antibody detection and be a useful non-invasive approach for immunodiagnosis of HCC. Therationale is that in sera from HCC patients who show autoantibody changes during progression fromchronic liver diseases to HCC, novel autoantibodies appearing during this progression will likely bereporters of events associated with tumorigenesis, and therefore autoantibodies can be used asprobes in SEREX and proteome-based approaches to identify antigens which are potentially involvedin malignant transformation.Short abstract: The majority of people with hepatocellular carcinoma (HCC) will die within 1 year of itsdetection. This high case-fatality rate can in part be attributed to lack of diagnostic methods that allowearly detection. In this study, we will determine whether a mini-array of multiple tumor-associatedantigens would enhance antibody detection and further develop a useful non-invasive approach for theearly detection of human HCC
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