Markers for the Early Detection of Ovarian Cancer

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant) Current technologies have been disappointing and have not resulted in diagnostic test suitable for clinical practice. The goal of this project is to detect antibodies that are produced by patients in reaction to proteins expressed in their ovarian tumors and use them as diagnostic biomarkers. The core of this project rests on research from the PI's lab in which he has developed a high throughput method to identify large numbers of epitopes that can be used to identify the presence of ovarian cancer by detecting the presence of auto-antibodies to tumor proteins in the serum of the test subject. These biomarkers are cloned without a preconceived notion of their function. The essential features of the approach are acknowledging the heterogeneous nature of any specific kind of cancer, departing from the reliance on any single marker for disease detection, and using specialized bioinformatics techniques to interpret the results. The concept employs pattern recognition of multiple markers as a diagnostic rather than any single marker. In the discovery phase, the serum antibodies have been detected by screening of large numbers of potential epitope targets on protein microarrays. We developed an effective screening test for early detection of ovarian cancer (OVCA) using cDNA T7 phage display libraries to isolate cDNAs coding for epitopes reacting with antibodies present specifically in the sera of patients with ovarian cancer. The isolation of these epitopes is achievable by our differential biopanning technology using human sera collected both from healthy controls and patients having ovarian cancer. We screen phage display tumor cell libraries from OVCA fro cDNAs of genes that bind immunoglobulin-G molecules (IgGs) present in OVCA patients' sera and do not bind to IgGs from normal sera. The serum reaction with large numbers of these epitopes is be detected in a highly parallel assay on protein microarrays. The principle is that we clone epitopes reacting with IgG in patients sera and use them to detect antibodies in sera to discriminate cancer and healthy subjects and whether we can detect disease prior to standard diagnosis.