TY - JOUR
T1 - Comparative genomics reveals distinct immune-oncologic pathways in African American Men with Prostate Cancer
AU - Awasthi, Shivanshu
AU - Berglund, Anders
AU - Abraham-Miranda, Julieta
AU - Rounbehler, Robert J.
AU - Kensler, Kevin
AU - Serna, Amparo
AU - Vidal, Adriana
AU - You, Sungyong
AU - Freeman, Michael R.
AU - Davicioni, Elai
AU - Liu, Yang
AU - Jeffrey Karnes, R.
AU - Klein, Eric A.
AU - Den, Robert B.
AU - Trock, Bruce J.
AU - Campbell, Joshua D.
AU - Einstein, David J.
AU - Gupta, Raavi
AU - Balk, Steven
AU - Lal, Priti
AU - Park, Jong Y.
AU - Cleveland, John L.
AU - Rebbeck, Timothy R.
AU - Freedland, Stephen J.
AU - Yamoah, Kosj
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Purpose: The role of immune-oncologic mechanisms of racial disparities in prostate cancer remains understudied. Limited research exists to evaluate the molecular underpinnings of immune differences in African American men (AAM) and European American men (EAM) prostate tumor microenvironment (TME). Experimental Design: A total of 1,173 radiation-na€ve radical prostatectomy samples with whole transcriptome data from the Decipher GRID registry were used. Transcriptomic expressions of 1,260 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 proinflammatory cytokines, IFNa, IFNg, TNFa signaling, ILs, and epithelial–mesenchymal transition. AAM TME has higher total immune content score (ICSHIGH) compared with 0 (37.8% vs. 21.9%, P ¼ 0.003). AAM tumors also have lower DNA damage repair and are genomically radiosensitive as compared with EAM. IFITM3 (IFN-inducible transmembrane protein 3) was one of the major proinflammatory genes overexpressed in AAM that predicted increased risk of biochemical recurrence selectively for AAM in both discovery [HRAAM ¼ 2.30; 95% confidence interval (CI), 1.21–4.34; P ¼ 0.01] and validation (HRAAM ¼ 2.42; 95% CI, 1.52–3.86; P ¼ 0.0001) but not in EAM. Conclusions: Prostate tumors of AAM manifest a unique immune repertoire and have significant enrichment of proinflammatory immune pathways that are associated with poorer outcomes. Observed immune-oncologic differences can aid in a genomically adaptive approach to treating prostate cancer in AAM.
AB - Purpose: The role of immune-oncologic mechanisms of racial disparities in prostate cancer remains understudied. Limited research exists to evaluate the molecular underpinnings of immune differences in African American men (AAM) and European American men (EAM) prostate tumor microenvironment (TME). Experimental Design: A total of 1,173 radiation-na€ve radical prostatectomy samples with whole transcriptome data from the Decipher GRID registry were used. Transcriptomic expressions of 1,260 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 proinflammatory cytokines, IFNa, IFNg, TNFa signaling, ILs, and epithelial–mesenchymal transition. AAM TME has higher total immune content score (ICSHIGH) compared with 0 (37.8% vs. 21.9%, P ¼ 0.003). AAM tumors also have lower DNA damage repair and are genomically radiosensitive as compared with EAM. IFITM3 (IFN-inducible transmembrane protein 3) was one of the major proinflammatory genes overexpressed in AAM that predicted increased risk of biochemical recurrence selectively for AAM in both discovery [HRAAM ¼ 2.30; 95% confidence interval (CI), 1.21–4.34; P ¼ 0.01] and validation (HRAAM ¼ 2.42; 95% CI, 1.52–3.86; P ¼ 0.0001) but not in EAM. Conclusions: Prostate tumors of AAM manifest a unique immune repertoire and have significant enrichment of proinflammatory immune pathways that are associated with poorer outcomes. Observed immune-oncologic differences can aid in a genomically adaptive approach to treating prostate cancer in AAM.
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U2 - 10.1158/1078-0432.CCR-20-2925
DO - 10.1158/1078-0432.CCR-20-2925
M3 - Article
C2 - 33037017
AN - SCOPUS:85100347431
SN - 1078-0432
VL - 27
SP - 320
EP - 329
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -