LCM & 2D PAGE in Early Detection of Pancreatic Cancer

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DESCRIPTION (provided by applicant): The goal of this application is to identify pancreatic cancer cell-specific antigens that are specifically recognized by sera from patients with pancreatic carcinoma and to establish a new area of research in the applicant's laboratory to investigate pancreatic cancer. The long-term goal of this research is to develop effective means to detect, screen, prevent, and treat pancreatic cancer in humans. Each year, 30,300 new cases of pancreatic cancer are detected in this country. Sadly, about the same number die per year from the disease due to difficulties in diagnosis, the intrinsic aggressive nature of the disease, and the unavailability of effective systemic treatment. Many genetic profiling studies and proteomic-based approaches have been used to identify altered genes, proteins or antigens in pancreatic cancer that could be used as biomarkers. Unfortunately, the use of entire biopsy specimens or cell cultures from pancreatic cancer patients led to identification of markers with low specificity for pancreatic cancer. Our laboratory recently applied new technologies in isolating pure cancer cells and identified pancreatic cancer antigens that reacted with sera from patients with pancreatic cancer and not with sera from healthy volunteers. Based on these results, we hypothesized that tumor cell-specific antigen(s) can be identified by screening pancreatic cancer cell-specific proteins for reactivity with autoantibodies from sera of pancreatic carcinoma patients. To test this, we recently used state-of-the-art technologies such laser capture microdissection (LCM), 2-dimensional gel electrophoresis (2D-PAGE), and Western blot analysis to identify tumor specific antigens. Here, we propose to identify pancreatic cancer cell-specific antigens that will react only with sera from patients with pancreatic cancer and not with sera from patients with other pancreatic diseases, patients with other malignancies (e.g. Gl and breast), and sera from healthy individuals. Our specific aims are: i) to identify carcinoma cell-specific antigen(s) that react with autoantibodies in sera from patients with pancreatic carcinoma, ii) to determine the specificity of the antigen(s) for pancreatic cancer, iii) to determine the identity of the pancreatic cancer cell-specific antigen(s). These cancer cell-specific antigens could be developed as biomarkers for early detection, screening, and targeted therapy of pancreatic cancer.