Abstract 1831: Identification of alpha-enolase and annexin as candidate tumor-associated antigens by immunoseroproteomic profiling of autoantibodies in African American and Caucasian men with prostate cancer

Abstract

Abstract 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 men (AA), with a mortality rate that is two-fold higher than in other ethnic groups. 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 in obese and young AA men. Therefore, there is a critical need for identifying additional minimally invasive PCa biomarkers, especially in high-risk populations such as AA men. Immunoseroproteomics is a powerful approach for profiling circulating autoantibodies targeting tumor-associated antigens (TAAs) in cancer patients. These autoantibodies may serve as “reporters” to tumorigenic events and potential diagnostic biomarkers relevant to tumor biology. Based on recent reports of racial differences in the immunobiology of PCa, we hypothesized that AA and CC men with PCa may produce different anti-TAA autoantibody profiles. To evaluate this hypothesis, total proteins from aggressive PCa cells were separated by one or two-dimensional (2D) gel electrophoresis and then probed by immunoblotting with sera from AA (n = 40) and CC (n = 50) PCa patients to identify immunoreactive protein bands or spots. Protein spots recognized by the patient sera were then excised from the 2D gels and analyzed by mass spectrometry to profile the anti-TAA autoantibody repertoire in a given patient. Sera from AA PCa patients showed stronger immunoreactivity against PC3 cell proteins than sera from the CC cohort when evaluated under identical conditions in immunoblots. A common immunoreactive band around 45-50kD was produced by several AA sera (n = 8), and by one CC serum, and subsequent analysis by mass spectrometry showed that it corresponded to alpha-enolase. Confirmation that the AA PCa sera recognized 47kD alpha-enolase was obtained by immunoblots showing that these sera recognized the same protein bands recognized by a monoclonal antibody to this protein. Some of these sera also reacted against annexin A2. Additional validation studies are currently under way. Alpha-enolase and annexin A2 have been recently identified as candidate plasminogen receptors with roles in PCa. Alpha-enolase has been shown to promote cancer aggressiveness properties and its expression in tumors is associated with poor clinical outcomes. Alpha-enolase is a promising candidate biomarker that if used in combination with other TAAs for autoantibody profiling in PCa might help in the early detection and management of PCa, particularly in AA men. Citation Format: Tino Wilson Sanchez, Kwame Agyeman, Saied Mirshahidi, Nathan Wall, Colwick Wilson, Susanne Montgomery, Carlos A. Casiano. Identification of alpha-enolase and annexin as candidate tumor-associated antigens by immunoseroproteomic profiling of autoantibodies in African American and Caucasian men with prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1831. doi:10.1158/1538-7445.AM2015-1831