Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence
Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry. Clinical follow-up revealed increased biochemical recurrence (BCR) among Black patients compared to White patients with high-grade PCa. Transcriptomic analysis identified differential alternative RNA splicing events (ARSs) between Black and White PCa patients. Genes undergoing genetic ancestry-concordant ARSs in high-grade or low-grade tumors involved cancer promoting genes. Most genes undergoing genetic ancestry-concordant ARSs did not exhibit differential aggregate gene expression or alternative polyadenylation. A number of the genetic ancestry-concordant ARSs associated with BCR; thus, genetic ancestry-concordant RNA splice variants may represent unique targets for PCa precision oncology.
Authors
- Jennifer A. Freedman (ORCID: https://orcid.org/0000-0001-6771-4161)
- Michael N. Ferrandino (ORCID: https://orcid.org/0000-0002-5097-0318)
- Muthana Al Abo (ORCID: https://orcid.org/0000-0001-6028-3688)
- Jiaoti Huang (ORCID: https://orcid.org/0000-0003-1195-1998)
- Lauren E. Howard (ORCID: https://orcid.org/0000-0003-3355-4483)
- Monika Anand (ORCID: https://orcid.org/0000-0001-8634-4952)
- Andrew J. Armstrong (ORCID: https://orcid.org/0000-0001-7012-1754)
- Shannon J. McCall (ORCID: https://orcid.org/0000-0003-3957-061X)
- Blair Thornburg
- Julie J.G. Kephart
- Daniel J. George (ORCID: https://orcid.org/0000-0002-0836-8542)
- Brant A. Inman (ORCID: https://orcid.org/0000-0002-6060-4485)
- Alison Clayton
- Terry Hyslop (ORCID: https://orcid.org/0000-0002-3930-8876)
- Steven R. Patierno (ORCID: https://orcid.org/0000-0003-0636-2128)
- Bonnie LaCroix (ORCID: https://orcid.org/0000-0002-6833-5267)
- Yuan Wu (ORCID: https://orcid.org/0000-0001-8925-555X)
- Shannon McGue (ORCID: https://orcid.org/0000-0002-3810-8629)
- Michael B. Rothberg (ORCID: https://orcid.org/0000-0003-2062-6329)
- Cary N. Robertson
- Judd W. Moul
- Wen-Chi Foo
- Thomas J. Polascik (ORCID: https://orcid.org/0000-0003-3666-1372)
- Thomas A. Esther
Institutions
- Western University (CA)
- Lawson Health Research Institute (CA)
- Thomas Jefferson University (US)
- Duke University (US)
- The Urology Center of Colorado (US)
- Compass (United States) (US)
- Tempus Labs (United States) (US)
- Duke Medical Center (US)
- Flatiron Health (United States) (US)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-01-29
- DOI
- https://doi.org/10.1038/s41698-025-00817-9
- Citations
- 2
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- U.S. Department of Defense
- Prostate Cancer Foundation
- Movember Foundation
- National Institutes of Health
- School of Medicine, Duke University
- National Institute on Minority Health and Health Disparities
- Duke Cancer Institute
- DOD Prostate Cancer Research Program