Abstract C159: Enolase autoantibodies in African American and European American patients with prostate cancer
Authors: Cheng Kai Wen , Ochoa Pedro T. , Alramadhan Zainab , Reeves Michael , Sanchez-Hernandez Evelyn S. , Lozano Diana , Montgomery Susanne , Mirshahidi Saied , Ambs Stefan , Hu Brian R. , Almaguel Frankis , Casiano Carlos A. 
Published: September 2024

Abstract
Prostate cancer (PCa) is the most common malignancy diagnosed in men in the U.S., with African American (AA) patients harboring high risk for more aggressive disease. Enolase (ENO) autoantibodies have been detected in patients with PCa, and race-related differential immunoreactivity to ENO in docetaxel-resistant (DR) PCa cells have been described between AA and European American (EA) patients. In this study we evaluated the frequency of autoantibodies to distinct ENO isoforms (ENO1 and ENO2) in AA and EA PCa patient sera and their corresponding associations with clinicopathological parameters. Human sera were obtained from patients with PCa (138 AA, 169 EA) and matched controls (100 AA, 100 EA). Clinicopathological parameters were available for the majority of patients. Immunoblotting was performed with docetaxel-sensitive (DS) and DR PCa cell lines to determine expression of ENO isoforms and neuroendocrine markers (e.g. chromogranin A and ENO2). ELISA was performed using recombinant ENO1 (rENO1) and ENO2 (rENO2) proteins as substrates to detect ENO1 and ENO2 autoantibodies, respectively, in patient sera. ELISA cut-off value was established to obtain 90% specificity (negative reactivity) in control sera. On immunoblots, ENO1 expression was robust and similar for both DS and DR cells. ENO2 expression was observed in DS cells but significantly reduced in DR cells. On ELISA, 65 PCa sera (21%) reacted with rENO1 above the cut-off value and 33 (11%) reacted with rENO2, compared to the predetermined 10% positive reactivity rate in the control cohort (p&lt;0.001, p=0.79, respectively). When stratified by race, 40 (29%) AA sera reacted with rENO1 compared to 25 (15%) EA sera (p=0.0025). There was no significant race-related differential immunoreactivity to rENO2. In the cohort of patients with clinicopathological data, 39 PCa sera (20%) reacted with rENO1 above the cut-off value and 26 (13%) reacted with rENO2 (p=0.0074, p=0.34, respectively). In this subgroup, there was no significant race-related differential immunoreactivity to rENO1 or rENO2. Overall survival and cancer-specific survival was significantly lower for PCa patients with high reactivity to rENO1 (p=0.062, p&lt;0.001, respectively). On multivariate analysis, AA race and high reactivity to rENO1 were significantly associated with lower overall survival. In addition, higher disease stage (III/IV) and high reactivity to rENO1 were associated with lower cancer-specific survival. In conclusion, ENO1 autoantibodies were detected at higher frequencies in AA and EA patients with PCa compared to matched controls and were associated with lower overall and cancer- specific survival. This may reflect higher tumor ENO1 expression in a subset of PCa patients with more aggressive disease. The presence of ENO1 autoantibodies appears to be a promising prognostic marker in PCa for both AA and EA patients, especially in high-risk neuroendocrine disease with limited diagnostic targets due to loss of PSMA expression.
Citation Format: Kai Wen Cheng, Pedro T. Ochoa, Zainab Alramadhan, Michael Reeves, Evelyn S. Sanchez-Hernandez, Diana Lozano, Susanne Montgomery, Saied Mirshahidi, Stefan Ambs, Brian R. Hu, Frankis Almaguel, Carlos A. Casiano. Enolase autoantibodies in African American and European American patients with prostate cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C159.