Abstract 2502: Immunoseroproteomic profiling of autoantibodies to tumor associated autoantigens in African American and Caucasian men with prostate cancer

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 compared to Caucasian (CC) men. This prompted us to initiate an immunoproteomic analysis of the anti-TAA autoantibody response in AA and CC men with PCa. We hypothesize the anti-TAA autoantibody response might be greater 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 initial studies, we screened aggressive PCa cell lysates with serum samples from AA (n=39) and CC (n=50) men. Early results showed the autoantibody response in the AA cohort had a greater autoantibody frequency and reactivity than the response in CC patients. Immunoproteomic analysis of select AA sera revealed alpha-enolase, fumarate hydratase, and annexin A11 as candidate TAAs in PCa. These proteins have been implicated in previous PCa studies. Additional validation will come from determining the frequency of the autoantibody response and the expression of candidate TAAs in PCa tissue microarrays. We are currently expanding our immunoseroproteomics analysis to sera from a larger cohort (n>200) of AA men and CC men (n>100) with and without PCa, stratified by age and cancer stage. Comparing the anti-TAA repertoire between AA and CC men with and without PCa will aid in the customization of TAA arrays for autoantibody profiling and lead to the identification of promising biomarkers for early PCa detection and monitoring of tumor progression in AA populations. Our approach may also help identify unique immunoserological signatures in AA and CC men to reveal biological determinants of PCa health disparities. Citation Format: Tino Wilson Sanchez, Saied Mirshahidi, Nathan Wall, Susanne Montgomery, Colwick Wilson, 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 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2502. doi:10.1158/1538-7445.AM2014-2502