Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence
Abstract 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 co...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00817-9 |
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| author | Muthana Al Abo Wen-Chi Foo Lauren E. Howard Shannon McGue Bonnie Lacroix Julie Kephart Angela Clayton Blair Thornburg Monika Anand Michael B. Rothberg Shannon J. McCall Jiaoti Huang Thomas A. Esther Judd W. Moul Michael N. Ferrandino Thomas J. Polascik Cary N. Robertson Brant A. Inman Andrew J. Armstrong Yuan Wu Terry Hyslop Daniel J. George Steven R. Patierno Jennifer A. Freedman |
| author_facet | Muthana Al Abo Wen-Chi Foo Lauren E. Howard Shannon McGue Bonnie Lacroix Julie Kephart Angela Clayton Blair Thornburg Monika Anand Michael B. Rothberg Shannon J. McCall Jiaoti Huang Thomas A. Esther Judd W. Moul Michael N. Ferrandino Thomas J. Polascik Cary N. Robertson Brant A. Inman Andrew J. Armstrong Yuan Wu Terry Hyslop Daniel J. George Steven R. Patierno Jennifer A. Freedman |
| author_sort | Muthana Al Abo |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-f71b2a94b7b94bafb91ba84913a923b0 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-f71b2a94b7b94bafb91ba84913a923b02025-02-02T12:06:36ZengNature Portfolionpj Precision Oncology2397-768X2025-01-019111610.1038/s41698-025-00817-9Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrenceMuthana Al Abo0Wen-Chi Foo1Lauren E. Howard2Shannon McGue3Bonnie Lacroix4Julie Kephart5Angela Clayton6Blair Thornburg7Monika Anand8Michael B. Rothberg9Shannon J. McCall10Jiaoti Huang11Thomas A. Esther12Judd W. Moul13Michael N. Ferrandino14Thomas J. Polascik15Cary N. Robertson16Brant A. Inman17Andrew J. Armstrong18Yuan Wu19Terry Hyslop20Daniel J. George21Steven R. Patierno22Jennifer A. Freedman23Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDepartment of Internal Medicine, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineFlatiron HealthTempus CompassDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineColorado UrologyDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDivision of Urology, Department of Oncology, Lawson Health Research Institute, Western UniversityDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDepartment of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson UniversityDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineDuke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of MedicineAbstract 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.https://doi.org/10.1038/s41698-025-00817-9 |
| spellingShingle | Muthana Al Abo Wen-Chi Foo Lauren E. Howard Shannon McGue Bonnie Lacroix Julie Kephart Angela Clayton Blair Thornburg Monika Anand Michael B. Rothberg Shannon J. McCall Jiaoti Huang Thomas A. Esther Judd W. Moul Michael N. Ferrandino Thomas J. Polascik Cary N. Robertson Brant A. Inman Andrew J. Armstrong Yuan Wu Terry Hyslop Daniel J. George Steven R. Patierno Jennifer A. Freedman Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence npj Precision Oncology |
| title | Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence |
| title_full | Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence |
| title_fullStr | Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence |
| title_full_unstemmed | Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence |
| title_short | Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence |
| title_sort | genetic ancestry concordant rna splicing in prostate cancer involves oncogenic genes and associates with recurrence |
| url | https://doi.org/10.1038/s41698-025-00817-9 |
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