This project brings together researchers who have established research track records in high-throughput platforms of carbohydrate microarrays, neoglycolipid (NGL) technology coupled with mass spectrometry for carbohydrate ligand discovery, flow cytometry (Hi-D FACS) for highly-sensitive detection of cell and serum markers, and the first international standard for detection of prostate-specific antigen (PSA). The thrust of this team is identification and characterization of immunological biomarkers and development of highly sensitive assays for clinical and research applications. The ultimate goal of this project is to identify novel serum biomarkers for detection of prostate cancer and monitoring of cancer progression. In preliminary investigations, they have identified a number of carbohydrate-based biomarkers in prostate cancers. In addition, they have detected autoantibodies to some of these using carbohydrate microarrays. They hypothesize that these aberrantly expressed carbohydrates are immunogenic and are able to induce specific autoantibodies in prostate cancer subjects. Detection of such antibodies in serum could allow detection of prostate cancer and its aggressive progression. In this project, collaborating group plan to examine their hypotheses by characterizing a large-collection of well-categorized serum and tissue specimens preserved in their prostate cancer tissue banks. They plan to 1) determine whether anti-carbohydrate autoantibodies specific for Mannose-clusters and other A/-glycans not normally expressed can distinguish between men with BPH and prostate cancer and/or predict the aggressive and progressive prostate cancers;2) determine whether serum antibodies specific for other carbohydrate autoantigens are present in prostate cancer subjects and evaluate their diagnostic and prognostic values;3) determine whether the presence of certain anti-carbohydrate antibodies in the serum of an individual correlates with the aberrant expression of corresponding glyco-epitopes in the prostate cancer;4) determine the carbohydrate O-glycan sequences of glyco-epitopes of HCA and other cancer-associated glycoproteins that are recognized by mAb AE3 and G1;and 5) establish highly sensitive and user-friendly immunoassays using novel serological markers to facilitate a large-scale clinical study of prostate cancer.
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