Abstract 2196: Prostate cancer: Immune-inflammation signature in men of African ancestry

Abstract

Abstract African American (AA) men have a 2 to 3 times higher prostate cancer mortality rates than European American (EA) men. Studies suggested that tumor biology may influence racial/ethnic survival and account for 24% of the disparities in PCa that remains even when controlled for access to care and stage at presentation. Additionally, men of African ancestry from the Caribbean and South America experience incidence and mortality rates similar to AA men, suggesting a possible ancestral basis for some of these expected outcomes. No study has currently assessed whether African descent men are affected by a systemic inflammatory process with changes in the immune system that increases the risk of lethal PCa. To assess the hypothesis that African ancestry drives aggressive prostate cancer and leads to genetic alterations with upregulation of unique immune-inflammatory signatures in men of African descent, we performed a genome-wide RNA sequencing analysis. We analyzed RNA isolated from FFPE tumor tissue obtained from 15 patients who self-reported as AA and 13 patients who self-reported as EA (n=28). To verify self-reported race, we used ADMIXTURE to generate a quantitative estimate of each individual ancestral composition. Notably, 14 patients who self-reported as AA also have a predominant African ancestry, particularly from African Caribbean's subpopulation, and one patient who self-reported as AA was actually Ad Mixed American. Furthermore, we conducted a descriptive statistical analysis of the study population; patients were stratified by race and pathology stage. Our results show that AA men are diagnosed with PCa at a younger age and higher pathology stage (≥ T2), contributing to a lower survival rate in AA. Gene-level expression was measured from STAR counts using Ensembl gene annotation. The resulting datasets were analyzed for differential gene expression and enriched pathways based on the patient's ancestry, race, and Gleason Score. Our analyses reveal that interferon-inducible genes (ISG15, IFT1, STAT1) are positively enriched (p-value 0.05), while neutrophil degranulation and Interleukins genes (IL8, CXCL8, KRTs, IL6, CXCL6) are negatively enriched (p-value 0.05) in AA men. These enriched gene sets may indicate that immune/inflammatory signatures play an important role in driving aggressive prostate cancer in AA. Additionally, we run GSEA-based on the immunological signature mode and used gene ontology function in EdgeR package; both showed that immune-related signaling pathways are enriched in AA men. These findings were confirmed in other RNA-Seq data sets attained from FFPE tissues. Similar immune/inflammatory patterns were observed in AA PCa cell lines (RC). Our study provides new insight into understanding how genetic ancestry and upregulation of unique immune-inflammatory signatures may contribute to PCa racial disparities in AA men cohorts from African ancestry. Citation Format: Isra A. Elhussin, Jason A. White, Tamaro S. Hudson, Moray J. Campbell, Chanita Hughes-Halbert, Stefan Ambs, Clayton Yates. Prostate cancer: Immune-inflammation signature in men of African ancestry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2196.