Abstract B03: Identification of alpha-enolase as a candidate tumor associated autoantigen in African American men with prostate cancer

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related male deaths in the U.S. PCa is diagnosed more frequently in African American (AA) men, who have a mortality rate that is two-fold higher than Caucasian (CC) men. The current diagnostic test for PCa relies on the detection of prostate specific antigen (PSA). Although this minimally invasive test has high sensitivity, its limited specificity leads to false positives and unnecessary biopsies. This test may also fail to recognize PCa in men with low PSA levels, especially obese AA men. Recent studies indicate that genes associated with immune function and autoimmunity are significantly upregulated in prostate tumors from AA men compared to CC. This led us to evaluate autoantibody responses to potential tumor-associated autoantigens (TAA) by immunoseroproteomic profiling of sera from AA and CC patients with PCa. There is a critical need to identify biomarkers to complement the PSA test, especially in high risk populations like AA men, and immunoseroproteomics offers a minimally invasive approach to detect early malignant processes that trigger the production of autoantibodies to TAA. These antibodies serve as “reporters” of tumorigenic events and can be assessed as potential diagnostic biomarkers relevant to tumor biology. One and two-dimensional gel electrophoresis of total protein lysates from aggressive PCa cell lines were probed with sera from AA (n=39) and CC (n=50) PCa patients, and immunoreactive spots were identified using mass spectrometry to profile the anti-TAA antibody repertoire in a given patient. We observed that sera from AA PCa patients showed elevated immunoreactivity than sera from CC patients, when normalized for the same cell line and experimental conditions. A prominent band of approximately 50 kD was recognized by several AA sera, and subsequent analysis by Orbitrap mass spectrometry showed that the autoantibodies in these sera recognized alpha-enolase. The 47kD alpha-enolase protein was identified as a target TAA in eight different AA PCa sera. Several other sera not evaluated by mass spectrometry also showed reactivity at this molecular weight. Alpha-enolase is a metabolic protein that is upregulated in several cancers including PCa. It plays an important role in tumor development and glucose metabolism, and its upregulation has been associated with poor clinical outcome. Alpha-enolase is a promising candidate biomarker whose inclusion in well-defined, PCa-specific TAA panels could help in the serological detection and management of PCa, particular in AA men. Citation Format: Tino Wilson Sanchez, Saied Mirshahidi, Nathan Wall, Colwick Wilson, Susanne Montgomery, Carlos A. Casiano. Identification of alpha-enolase as a candidate tumor associated autoantigen in African American men with prostate cancer. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B03.