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Racial variation in the advanced prostate cancer genome

Feng, Emily M. ; Vo-Phamhi, Jenny ; Subramanian, Aishwarya N. ; Dias, Mikhail ; Foye, Adam ; Vinson, Jake ; Hong, Julian C. ; Freedland, Stephen J. ; Alumkal, Joshi J. and Beltran, Himisha , et al. (2025) In Prostate Cancer and Prostatic Diseases
Abstract

Background: Racial differences in metastatic castration-resistant prostate cancer (mCRPC) genomes have not yet been fully studied. We aimed to investigate transcriptomic, mutational, and clinical differences by race in a large multi-institutional cohort of men with mCRPC. Methods: Genomic and clinicopathologic data from four mCRPC tumor biopsy cohorts were obtained and aggregated. Gene set enrichment analyses were performed to assess pathway-level differences in gene expression by patient race. DNA alteration frequencies of known prostate cancer driver genes and clinical outcomes were compared across racial groups. Results: In our cohort of 445 men with mCRPC, tumors from African American patients (N = 26) demonstrated higher expression... (More)

Background: Racial differences in metastatic castration-resistant prostate cancer (mCRPC) genomes have not yet been fully studied. We aimed to investigate transcriptomic, mutational, and clinical differences by race in a large multi-institutional cohort of men with mCRPC. Methods: Genomic and clinicopathologic data from four mCRPC tumor biopsy cohorts were obtained and aggregated. Gene set enrichment analyses were performed to assess pathway-level differences in gene expression by patient race. DNA alteration frequencies of known prostate cancer driver genes and clinical outcomes were compared across racial groups. Results: In our cohort of 445 men with mCRPC, tumors from African American patients (N = 26) demonstrated higher expression of MYC pathway genes (FDR q = 0.03) and lower expression of IFN-γ, IL-6/JAK/STAT3, and inflammatory pathway genes (FDR q < 0.001) compared to tumors from European American patients. TMPRSS2:ERG gene fusions were observed more frequently in tumors from European American compared to African American patients (41% vs. 11%, P = 0.015). Asian patients (N = 9) and other racial groups comprised a small minority of our cohort. No differences in overall survival were noted across racial groups. Conclusions: Despite demonstrating similar clinical outcomes, cancers from African Americans display distinct tumor biology. Specifically, we observed racial differences in expression of prostate cancer driver gene pathways (including potential clinically actionable pathways of IFN-γ and JAK/STAT) and DNA alterations, including TMPRSS2:ERG gene fusion. Our findings highlight the importance of racial diversity in future genomic profiling and clinical trials efforts.

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publication status
epub
subject
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Prostate Cancer and Prostatic Diseases
publisher
Nature Publishing Group
external identifiers
  • pmid:40164700
  • scopus:105001526681
ISSN
1365-7852
DOI
10.1038/s41391-025-00949-w
language
English
LU publication?
yes
id
683c65d4-6d10-4b6f-96cc-3caf314dbc2d
date added to LUP
2025-09-04 09:21:01
date last changed
2025-09-05 03:00:07
@article{683c65d4-6d10-4b6f-96cc-3caf314dbc2d,
  abstract     = {{<p>Background: Racial differences in metastatic castration-resistant prostate cancer (mCRPC) genomes have not yet been fully studied. We aimed to investigate transcriptomic, mutational, and clinical differences by race in a large multi-institutional cohort of men with mCRPC. Methods: Genomic and clinicopathologic data from four mCRPC tumor biopsy cohorts were obtained and aggregated. Gene set enrichment analyses were performed to assess pathway-level differences in gene expression by patient race. DNA alteration frequencies of known prostate cancer driver genes and clinical outcomes were compared across racial groups. Results: In our cohort of 445 men with mCRPC, tumors from African American patients (N = 26) demonstrated higher expression of MYC pathway genes (FDR q = 0.03) and lower expression of IFN-γ, IL-6/JAK/STAT3, and inflammatory pathway genes (FDR q &lt; 0.001) compared to tumors from European American patients. TMPRSS2:ERG gene fusions were observed more frequently in tumors from European American compared to African American patients (41% vs. 11%, P = 0.015). Asian patients (N = 9) and other racial groups comprised a small minority of our cohort. No differences in overall survival were noted across racial groups. Conclusions: Despite demonstrating similar clinical outcomes, cancers from African Americans display distinct tumor biology. Specifically, we observed racial differences in expression of prostate cancer driver gene pathways (including potential clinically actionable pathways of IFN-γ and JAK/STAT) and DNA alterations, including TMPRSS2:ERG gene fusion. Our findings highlight the importance of racial diversity in future genomic profiling and clinical trials efforts.</p>}},
  author       = {{Feng, Emily M. and Vo-Phamhi, Jenny and Subramanian, Aishwarya N. and Dias, Mikhail and Foye, Adam and Vinson, Jake and Hong, Julian C. and Freedland, Stephen J. and Alumkal, Joshi J. and Beltran, Himisha and Morrissey, Colm and Nelson, Peter S. and Chinnaiyan, Arul M. and Aggarwal, Rahul and Small, Eric J. and Quigley, David A. and Sjöström, Martin and Zhao, Shuang G. and Chen, William S.}},
  issn         = {{1365-7852}},
  language     = {{eng}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Prostate Cancer and Prostatic Diseases}},
  title        = {{Racial variation in the advanced prostate cancer genome}},
  url          = {{http://dx.doi.org/10.1038/s41391-025-00949-w}},
  doi          = {{10.1038/s41391-025-00949-w}},
  year         = {{2025}},
}