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

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.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2020 Oct 09 [Epub ahead of print]

Shivanshu Awasthi, Anders E Berglund, Julieta Abraham-Miranda, Robert J Rounbehler, Kevin H Kensler, Amparo N Serna, Adriana C Vidal, Sungyong You, Michael R Freeman, Elai Davicioni, Yang Liu, Jeffrey R Karnes, Eric A Klein, Robert B Den, Bruce J Trock, Joshua D Campbell, David J Einstein, Raavi Gupta, Steven P Balk, Priti Lal, Jong Y Park, John L Cleveland, Timothy R Rebbeck, Stephen J Freedland, Kosj Yamoah

Cancer Epidemiology, Moffitt Cancer Center., Department of Biostatistics and Bioinformatics, Division of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute., Department of Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute., Division of Population Sciences, Dana-Farber Cancer Institute., Surgery, Cedars-Sinai Medical Center., Department of Surgery & Biomedical Sciences, Cedars-Sinai Medical Center., Decipher Biosciences Inc., Decipher Biosciences., Urology, Mayo Clinic., Glickman Urological and Kidney Institute, Cleveland Clinic., Radiation Oncology, Thomas Jefferson University., The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine., Medicine, Boston University School of Medicine., Medicine, Beth Israel Deaconess Medical Center., Pathology, State University of New York Downstate Medical Center., Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center., Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania., Department of Tumor Biology, Moffitt Cancer Center and Research Institute., Medical Oncology, Dana-Farber Cancer Institute., Cancer Epidemiology and Radiation Oncology, H Lee Moffitt Cancer Center & Research Institute .

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