Abstract LB146: Elevated autoantibody response to enolase-1 is associated with poor overall survival in African American patients with prostate cancer

Abstract Prostate Cancer (PCa) remains the second leading cause of male cancer-related deaths in the U.S., with men of African ancestry (AA) exhibiting disproportionately higher mortality rates compared to European American (EA) men. Emerging evidence suggests that race-related immunobiological variations in PCa patients may contribute to disparities in tumor aggressiveness and clinical outcomes. This study explored the autoantibody response to the glycolytic enzymes Enolase-1 (ENO1) and -2 (ENO2) in AA and EA PCa patients. Based on prior research, we hypothesized that ENO1 and ENO2 are targets of autoantibodies in PCa patients and that these immune responses differ in frequency, levels, and clinical associations between AA and EA patients. Gene Expression Profiling Interactive Analysis (GEPIA) revealed elevated ENO1 expression in primary PCa, while ENO2 expression remained unchanged. Given that increased ENO1 expression may elicit an anti-tumor autoantibody response, we used ELISA to evaluate the prevalence of serum autoantibodies against purified ENO1 and ENO2 in PCa patients (n=307) and non-PCa controls (n=200). Our findings revealed significantly higher frequency and levels of ENO1 autoantibodies in PCa patients compared to controls (p<0.05), whereas ENO2 autoantibody frequency and levels were not significantly different between the two groups. However, stratifying PCa patients by self-reported racial groups uncovered significantly higher levels of ENO1 (p<0.001) and ENO2 (p<0.001) autoantibodies in AA patients compared to EA patients. ELISA results were confirmed by multiplex Western blotting. Kaplan-Meier survival and logistic regression analyses indicated that elevated ENO1 autoantibody levels, but not ENO2, were associated with poorer overall and cancer-specific patient survival, as well as advanced tumor stage and AA race. These results align with the growing recognition of race-related differences in PCa immunobiology. The heightened anti-ENO1 response observed in AA PCa patients may also reflect the presence of more aggressive, metabolically active tumors. Future studies will focus on the functional implications of patient-derived ENO1 and ENO2 autoantibodies, using proliferation, migration, invasion, clonogenic, tumorsphere, and metabolic assays, to determine their anti-cancer properties in racially distinct pre-clinical PCa models. Citation Format: Kai Wen Cheng, Pedro Ochoa, Alfonso Duran, Zainab Alramadhan, Michael Reeves, Diana Lozano, Evelyn Sanchez-Hernandez, Saied Mirshahidi, Susan Montgomery, Brain Hu, Frankis Almaguel, Stefan Ambs, Carlos A. Casiano. Elevated autoantibody response to enolase-1 is associated with poor overall survival in African American patients with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB146.