Abstract C10: Immunoseroproteomic profiling of autoantibodies to tumor-associated autoantigens in African American and Caucasian men with prostate cancer

Abstract

Abstract Cancer-associated serum autoantibodies are generally considered as “sensors” of molecular events associated with tumorigenesis, and thus constitute promising biomarkers for cancer detection and management, as well as tools for the identification of novel oncoproteins. Immunoseroproteomics is a standard approach for the identification of serum autoantibodies reacting with tumor-associated antigens (TAA) in human cancer populations. This approach entails using one- and two-dimensional gel electrophoresis of proteins from aggressive PCa cell lines, coupled with immunoblotting and mass spectrometry, to characterize the anti-TAA antibody repertoire in a given patient. Immunoseroproteomics has been applied mostly to cancer patients of European and Asian ancestry, and has not been used in African American (AA) patients with PCa. AA men show a disproportionately high incidence and mortality of PCa, compared to other ethnic groups, and display more aggressive tumors developing at a younger age. Recent epidemiological studies suggest that after adjusting for socioeconomic and health care-related factors, these disparities still persist, pointing to biological factors as contributors to these disparities. Growing evidence indicates that genes associated with immune function and autoimmunity are dysregulated in prostate tumors from AA men compared to Caucasian (CC) men. This prompted us to initiate a comprehensive analysis and comparison of the anti-TAA autoantibody response in AA and CC men with PCa by immunoproteomics. We hypothesized that this immune response might be augmented in AA patients with PCa, and that it could be used to identify novel blood biomarkers for early screening and management of the disease in AA men. In initial studies, we screened by immunoblotting of aggressive PCa cell lysates randomly selected serum samples from AA (n=10) and CC (n=13) men) with PCa. The initial results indicated that the autoantibody response in the AA cohort was much more robust in terms of autoantibody frequency and strength of reactivity than the response in CC patients. We used selected AA sera to identify novel TAA by immunoseroproteomics. Our initial analysis identified alpha enolase, fumarate hydratase, and annexin A1 as candidate TAAs in PCa. These proteins have been implicated in PCa in previous studies. Additional validation will be achieved by determining the frequency of the autoantibody response and the expression of these and other identified TAAs in PCa tissue microarrays. We are currently expanding our immunoseroproteomics analysis to sera from larger cohorts of AA and CC men (n>200 per group) with and without PCa, stratified by age and cancer stage. Our immunoproteomics approach will aid in the customization of TAA arrays for autoantibody profiling, leading to the identification of promising biomarkers for early PCa detection and monitoring tumor progression in the AA population. This approach may also reveal immune determinants underlying PCa health disparities. Citation Format: Tino W. Sanchez, Saied Mirshahidi, Nathan R. Wall, Colwick Wilson, Susanne Montgomery, Carlos A. Casiano. Immunoseroproteomic profiling of autoantibodies to tumor-associated autoantigens in African American and Caucasian men with prostate cancer. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C10. doi:10.1158/1538-7755.DISP13-C10