在平等的环境中，黑人男性患前列腺癌 (PC) 的风险更高，并且比白人男性患前列腺癌的级别更高。本研究旨在确定患有 PC 的黑人和白人之间的差异转录调控。我们对达勒姆退伍军人事务医疗中心治疗的 305 名黑人和 238 名白人进行了根治性前列腺切除术组织块的微阵列分析。通过差异表达、基因集富集分析、主调控因子分析和网络建模来比较不同种族的基因表达。使用基因表达综合 (GEO) 数据库中提供的外部数据集对研究结果进行了验证。第一个是由 1152 名前列腺癌患者（596 名黑人，556 名白人）组成的多机构队列，具有微阵列数据（GEO ID：GSE169038）。第二个是由 106 名患者（22 名黑人、48 名白人、36 名未知种族男性）组成的埃默里队列，具有 RNA 测序数据（GEO ID：GSE54460）。此外，我们使用来自黑人和白人的配对 AR ChIP-Seq 数据集（GEO ID：GSE18440 和 GSE18441）分析了雄激素受体 (AR) 染色质结合谱。我们鉴定了黑人和白人之间的 871 个差异表达基因。白人男性的 MYC 相关通路活性较高，而黑人男性的炎症、类固醇激素反应和癌症进展相关通路的活性增加。我们进一步确定了黑人患者中排名前10位的转录因子（TF），它们形成了以AR为中心的转录调控网络。在多个队列和 PC 分子亚型中，黑人与白人的该网络和通路的活动显着不同。这些发现表明黑人和白人的 PC 具有不同的肿瘤转录谱。此外，以 AR 为中心的高度互动的 TF 网络驱动着黑人男性的差异基因表达。需要进行更多研究来了解转录调控元件的这些差异对 PC 健康差异的影响程度。© 2024。这是美国政府的作品，在美国不受版权保护；外国版权保护可能适用。

Black men are at a higher risk of prostate cancer (PC) diagnosis and present with more high-grade PC than White men in an equal access setting. This study aimed to identify differential transcriptional regulation between Black and White men with PC.We performed microarray of radical prostatectomy tissue blocks from 305 Black and 238 White men treated at the Durham Veterans Affairs Medical Center. Differential expression, gene set enrichment analysis, master regulator analysis, and network modeling were conducted to compare gene expression by race. Findings were validated using external datasets that are available in the Gene Expression Omnibus (GEO) database. The first was a multi-institutional cohort of 1152 prostate cancer patients (596 Black, 556 White) with microarray data (GEO ID: GSE169038). The second was an Emory cohort of 106 patients (22 Black, 48 White, 36 men of unknown race) with RNA-seq data (GEO ID: GSE54460). Additionally, we analyzed androgen receptor (AR) chromatin binding profiles using paired AR ChIP-Seq datasets from Black and White men (GEO IDs: GSE18440 and GSE18441).We identified 871 differentially expressed genes between Black and White men. White men had higher activity of MYC-related pathways, while Black men showed increased activity of inflammation, steroid hormone responses, and cancer progression-related pathways. We further identified the top 10 transcription factors (TFs) in Black patients, which formed a transcriptional regulatory network centered on the AR. The activities of this network and the pathways were significantly different in Black vs. White men across multiple cohorts and PC molecular subtypes.These findings suggest PC in Black and White men have distinct tumor transcriptional profiles. Furthermore, a highly interactive TF network centered on AR drives differential gene expression in Black men. Additional study is needed to understand the degree to which these differences in transcriptional regulatory elements contribute to PC health disparities.© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.