Department of Cancer Epidemiology, H Lee Moffitt Cancer Center & Research Institutes, Tampa, Florida.
Department of Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center & Research Institutes, Tampa, Florida.
Clin Cancer Res. 2021 Jan 1;27(1):320-329. doi: 10.1158/1078-0432.CCR-20-2925. Epub 2020 Oct 9.
The role of immune-oncologic mechanisms of racial disparities in prostate cancer remains understudied. Limited research exists to evaluate the molecular underpinnings of immune differences in African American men (AAM) and European American men (EAM) prostate tumor microenvironment (TME).
A total of 1,173 radiation-naïve radical prostatectomy samples with whole transcriptome data from the Decipher GRID registry were used. Transcriptomic expressions of 1,260 immune-specific genes were selected to assess immune-oncologic differences between AAM and EAM prostate tumors. Race-specific differential expression of genes was assessed using a rank test, and intergene correlational matrix and gene set enrichment was used for pathway analysis.
AAM prostate tumors have significant enrichment of major immune-oncologic pathways, including proinflammatory cytokines, IFNα, IFNγ, TNFα signaling, ILs, and epithelial-mesenchymal transition. AAM TME has higher total immune content score (ICS) compared with 0 (37.8% vs. 21.9%, = 0.003). AAM tumors also have lower DNA damage repair and are genomically radiosensitive as compared with EAM. (IFN-inducible transmembrane protein 3) was one of the major proinflammatory genes overexpressed in AAM that predicted increased risk of biochemical recurrence selectively for AAM in both discovery [HR = 2.30; 95% confidence interval (CI), 1.21-4.34; = 0.01] and validation (HR = 2.42; 95% CI, 1.52-3.86; = 0.0001) but not in EAM.
Prostate tumors of AAM manifest a unique immune repertoire and have significant enrichment of proinflammatory immune pathways that are associated with poorer outcomes. Observed immune-oncologic differences can aid in a genomically adaptive approach to treating prostate cancer in AAM.
种族差异导致的前列腺癌的免疫肿瘤机制仍有待深入研究。目前，关于非裔美国男性（AAM）和欧洲裔美国男性（EAM）前列腺肿瘤微环境（TME）中免疫差异的分子基础的研究有限。
共使用了来自 Decipher GRID 注册中心的 1173 例放射治疗初治根治性前列腺切除术样本，这些样本具有全转录组数据。选择了 1260 个免疫特异性基因的转录组表达，以评估 AAM 和 EAM 前列腺肿瘤之间的免疫肿瘤学差异。使用秩检验评估基因的种族特异性差异表达，并使用基因间相关矩阵和基因集富集进行通路分析。
AAM 前列腺肿瘤中存在显著的主要免疫肿瘤途径富集，包括促炎细胞因子、IFNα、IFNγ、TNFα 信号、ILs 和上皮-间充质转化。与 EAM 相比，AAM 的 TME 具有更高的总免疫含量评分（ICS）（37.8%对 21.9%， = 0.003）。与 EAM 相比，AAM 肿瘤的 DNA 损伤修复能力更低，且具有基因组放射敏感性。IFN 诱导跨膜蛋白 3（IFN-inducible transmembrane protein 3）是 AAM 中过度表达的主要促炎基因之一，该基因选择性地预测了 AAM 患者的生化复发风险增加，在发现阶段（HR=2.30；95%置信区间[CI]，1.21-4.34； = 0.01）和验证阶段（HR=2.42；95% CI，1.52-3.86； = 0.0001）均如此，但在 EAM 中则不然。
AAM 的前列腺肿瘤表现出独特的免疫谱，并且存在丰富的促炎免疫途径，这些途径与较差的预后相关。观察到的免疫肿瘤学差异可以帮助我们在基因组上适应治疗 AAM 中的前列腺癌。
