Abstract PR002: SPOP mutation is associated with higher immunogenicity in African American men compared to European American men with prostate cancer

Abstract

Abstract In the United States, African American men (AAM) are diagnosed with more aggressive PCa at an earlier age and clinically advanced disease than European American men (EAM). These disparities are a result of a complex interplay between genetics, socioeconomic, and environmental factors, as well as access to healthcare which leads to differences in the disease risk and outcomes. Furthermore, men of African ancestry from the Caribbean and South America, as well as West Africa demonstrate incidence and mortality rates similar to AA men suggesting a possible ancestral basis for some of these expected outcomes. Moreover, the tumor microenvironment plays an essential role in tumor progression, aggressiveness, therapeutic response, and patient outcomes. Specifically, African American prostate tumors predominantly have upregulation of immune-inflammatory gene signature that has a critical role in driving aggressive PCa in this cohort. Here we hypothesize that African Ancestry drives aggressive PCa and lead to genetic alterations characterized by upregulation of unique Immune-inflammatory signature and higher immunogenicity in AAM of African descent. Our study provides new perspectives on the fact that men of African descent are affected by immune-inflammatory process characterized by changes in the immunogenicity that increases the risk of lethal PCa. We performed genome-wide sequencing (Whole-Exome Sequences (WES) and RNA sequences), for a total of (n= 72) patients obtained from treatment-naive PCa who self-reported their race (16 AAM, 25 EAM, 1 Asian, 30 Un-Reported Race (URR)). The total sequenced samples for the 72 patients are 119 samples (54 WES, 65 RNA), out of these 119, 47 samples have matched WES with RNA-Seq. Most of our cohorts who self-reported as AA, their ancestry assigned to African Ancestry (Ancestry proportion > 70%) with either Bantu subpopulation in Sub-Saharan area (western central Africa) and/or Yoruba (Nigeria) subpopulation. Interestingly, when we divided our samples based on PD-L1 expression (immunogenicity), patients with high PD-L1 have higher expression of CD8 T cells that co-express PD-1 compared to patients with low PD-L1. These results may indicate that African ancestry, immune inflammation signatures as well as PCa immunogenicity collectively play an important role in driving aggressive prostate cancer in AA. Moreover, our WES analysis revealed that patients with high African Ancestry associated with mutations such as AR-related mutation with SPOP mutation on the top mutations (higher in African Ancestry patients) as well as FOXA1, PTEN, TP53, and EPHB2. This study's findings could lead to new therapeutic strategies using anti-inflammatory drugs and immune modulators to decrease the disease burden among men globally, especially among men at high risk for PCa, such as AA men. Citation Format: Isra A. Elhussin, Melissa B. Davis, Moray J. Campbell, Stefan Ambs, Isaac Kim, Clayton Yates. SPOP mutation is associated with higher immunogenicity in African American men compared to European American men with prostate cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR002.