Ovarian cancer is the fourth leading cause of cancer-related deaths in women. Although significant progress has been made in its treatment, long-term survival has not changed significantly, due to inadequate early diagnostic approaches. The objective of this project is to develop a diagnostic assay for the early detection of ovarian cancer based on the identification and quantitation of tumor-reactive IgG, specifically against transformation-linked aberrant gene products. In human and experimental animal tumors, tumor-reactive antibodies can be demonstrated prior to the appearance of discernable tumors or the detection of circulating tumor antigens. The presence of circulating tumor-reactive IgG has been correlated with poor prognosis. Molecular biologic techniques have shown promise in detecting early gene mutations associated with the development of lung cancer; however, these techniques rely on the acquisition of transformed cells for analysis. Our studies have shown that, since immune recognition appears to be a direct consequence of cancer-linked genetic changes resulting in alterations within these proteins, the presence of reactive IgG provides an early marker of cancer-associated gene aberrations. This diagnostic assay is based on our patented diagnostic use of reactive antibodies combined with recognition of specific gene products, which have been demonstrated to be altered in ovarian cancer patients. Genetic alterations, resulting in altered proteins, have been demonstrated in tumor suppressor and growth regulatory genes. This study will analyze the recognition of specific intracellular proteins by autoantibodies from ovarian cancer patients and correlating this recognition with stage of disease. This project will also combine proteomics and autoreactivity to ovarian cancer-derived cellular proteins to identify novel components to provide additional tumor specificity. Since autoreactive IgGs are markers of gene alterations, the timing of their appearance will also provide information on specific genetic changes in cancer development and progression. Ultimately, antigenic proteins, linked with histologic type and stage of disease, will be combined into the development of protein arrays to screen for circulating reactive IgG as an early diagnostic test.
