Comparative genomics reveals distinct immune-oncologic pathways in African American men with prostate cancer

Clin Cancer Res. 2020 Oct 9:clincanres.2925.2020. doi: 10.1158/1078-0432.CCR-20-2925. Online ahead of print.

ABSTRACT

Purpose The role of immune-oncologic mechanisms of racial disparities in prostate cancer (PCa) remains understudied. Limited research exists to evaluate the molecular underpinnings of immune differences in African American (AAM) and European American (EAM) prostate tumor microenvironment (TME). Experimental Design A total of 1,173 radiation naïve radical prostatectomy samples with whole transcriptome data from the Decipher GRIDTM registry was used. Transcriptomic expressions of 1260 immune specific genes were selected to assess immune-oncologic differences between AAM and EAM prostate tumors. Race-specific differential expression of genes was assessed using a rank test, and intergene correlational matrix and gene set enrichment was used for pathway analysis. Results AAM prostate tumors have significant enrichment of major immune-oncologic pathways including pro-inflammatory cytokines, IFN-α, IFN-γ and TNF-α signaling, interleukins, and EMT. AAM TME has higher total immune content score (ICSHIGH) compared to EAM (37.8% vs 21.9%, p = 0.003). AAM tumors also have lower DNA damage repair and are genomically radiosensitive as compared to EAM. IFITM3 was one of the major pro-inflammatory gene overexpressed in AAM that predicted for increased risk of biochemical recurrence selectively for AAM in both discovery (HRAAM = 2.30, 95% CI, 1.21 – 4.34, p = 0.01) and validation (HRAAM = 2.42, 95% CI, 1.52 – 3.86, p = 0.0001) but not in EAM. Conclusions Prostate tumors of AAM manifest a unique immune repertoire and have significant enrichment of pro-inflammatory immune pathways that are associated with poorer outcomes. Observed immune-oncologic differences can aide in a genomically adaptive approach to treating PCa in AAM.

PMID:33037017 | DOI:10.1158/1078-0432.CCR-20-2925