Feng Emily M, Vo-Phamhi Jenny, Subramanian Aishwarya N, Dias Mikhail, Foye Adam, Vinson Jake, Hong Julian C, Freedland Stephen J, Alumkal Joshi J, Beltran Himisha, Morrissey Colm, Nelson Peter S, Chinnaiyan Arul M, Aggarwal Rahul, Small Eric J, Quigley David A, Sjöström Martin, Zhao Shuang G, Chen William S
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Prostate Cancer Prostatic Dis. 2025 Mar 31. doi: 10.1038/s41391-025-00949-w.
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.
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.
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.
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.
转移性去势抵抗性前列腺癌（mCRPC）基因组中的种族差异尚未得到充分研究。我们旨在调查一个大型多机构mCRPC男性队列中不同种族之间的转录组、突变和临床差异。
获取并汇总了来自四个mCRPC肿瘤活检队列的基因组和临床病理数据。进行基因集富集分析以评估不同种族患者基因表达的通路水平差异。比较了不同种族组已知前列腺癌驱动基因的DNA改变频率和临床结局。
在我们445例mCRPC男性队列中，与非裔美国患者相比，来自欧洲裔美国患者的肿瘤中MYC通路基因表达更高（FDR q = 0.03），而IFN-γ、IL-6/JAK/STAT3和炎症通路基因表达更低（FDR q < 0.001）。与非裔美国患者相比，在欧洲裔美国患者的肿瘤中更频繁观察到TMPRSS2:ERG基因融合（41%对11%，P = 0.015）。亚洲患者（N = 9）和其他种族组在我们的队列中占少数。不同种族组之间未观察到总生存期差异。
尽管临床结局相似，但非裔美国人的癌症表现出独特的肿瘤生物学特性。具体而言，我们观察到前列腺癌驱动基因通路（包括潜在可用于临床的IFN-γ和JAK/STAT通路）的表达以及DNA改变（包括TMPRSS2:ERG基因融合）存在种族差异。我们的发现凸显了种族多样性在未来基因组分析和临床试验中的重要性。
