Al Abo Muthana, Foo Wen-Chi, Howard Lauren E, McGue Shannon, Lacroix Bonnie, Kephart Julie, Clayton Angela, Thornburg Blair, Anand Monika, Rothberg Michael B, McCall Shannon J, Huang Jiaoti, Esther Thomas A, Moul Judd W, Ferrandino Michael N, Polascik Thomas J, Robertson Cary N, Inman Brant A, Armstrong Andrew J, Wu Yuan, Hyslop Terry, George Daniel J, Patierno Steven R, Freedman Jennifer A
Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of Medicine, Durham, NC, 27710, USA.
Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.
NPJ Precis Oncol. 2025 Jan 29;9(1):30. doi: 10.1038/s41698-025-00817-9.
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.
与其他种族和族裔的男性相比，黑人男性患前列腺癌（PCa）的比例过高。比较黑人和白人患者中PCa的分子特征有可能识别出新的精准医学干预措施的开发靶点。在此，我们对自我报告的黑人和白人PCa患者的前列腺肿瘤及配对的肿瘤旁正常组织进行了转录组分析，并估计了患者的遗传血统。临床随访显示，与患有高级别PCa的白人患者相比，黑人患者的生化复发（BCR）增加。转录组分析确定了黑人和白人PCa患者之间不同的可变RNA剪接事件（ARSs）。在高级别或低级别肿瘤中经历与遗传血统一致的ARSs的基因涉及癌症促进基因。大多数经历与遗传血统一致的ARSs的基因没有表现出差异总基因表达或可变聚腺苷酸化。一些与遗传血统一致的ARSs与BCR相关；因此，与遗传血统一致的RNA剪接变体可能代表PCa精准肿瘤学的独特靶点。
