PO.PS01.03 · 人群科学
前列腺癌免疫图谱和基因特征的族裔差异
Ethnic differences in the immune landscape and gene signature in prostate cancer
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摘要 Abstract
中文摘要
前列腺癌是一种生物学和临床上高度异质性的疾病，其发病率和死亡率在不同种族和族裔群体间差异显著。在黑人美国（BA）男性中，前列腺癌的发病率约高出60%，死亡率是白人美国（WA）男性的两到三倍。这些差异是多因素的，涉及生物学和社会决定因素，如遗传易感性、合并症、社会经济地位、环境暴露和文化影响。虽然这些因素显然会影响疾病结局，但越来越多的证据强调，肿瘤免疫微环境及其相关基因特征在塑造前列腺癌生物学和进展中起着关键作用。为研究肿瘤免疫基因特征的族裔差异，我们分析了来自35例未经治疗患者的根治性前列腺切除标本的转录组数据，包括20例BA和15例WA男性。使用EPIC、xCell和Ingenuity通路分析（Ingenuity Pathway Analysis）检查肿瘤和邻近正常组织的基因表达谱。通过秩检验确定差异基因表达，并通过单变量Cox回归评估预后关联。WA肿瘤富集与神经炎症和氧化磷酸化相关的通路，包括IL-8信号、神经炎症、树突状细胞成熟、氧化磷酸化、T细胞中的PKCθ信号以及NFAT介导的免疫调节，而PPAR和PD-1/PD-L1通路活性较低。相比之下，BA肿瘤的特征是促炎和免疫调节通路的激活增强；表现出CREB信号、Th1/Th2激活、树突状细胞成熟、IL-17和TREM1信号以及IL-17A/F介导的细胞因子产生升高，而PD-1/PD-L1、ILK、IL-3、VEGF和B细胞受体通路活性降低。13种免疫细胞类型显示出种族特异性的基因表达模式，包括ARG1、FA2H、FBXO39、IGLL3P、KLKB1、MERTK、SEMA3G和TRPV5在WA肿瘤中显著表达，而ARSL、BAALC、CCL23、EPHA2、IGFL2、KRT5、NTM和NDP在BA肿瘤中上调。这些结果揭示了BA和WA前列腺肿瘤之间不同的免疫-肿瘤学图谱，突出了BA男性中促炎通路的富集，并强调了族裔特异性、基因组指导治疗的机会。
查看英文原文 English abstract
Prostate cancer is a biologically and clinically heterogeneous disease, with incidence and mortality rates that vary substantially across racial and ethnic groups. Among Black American (BA) men, the incidence of prostate cancer is approximately 60% higher, and the mortality rate is two to three times greater than that observed in White American (WA) men. These disparities are multifactorial, involving both biological and social determinants such as genetic predisposition, comorbidities, socioeconomic status, environmental exposures, and cultural influences. While these factors obviously contribute to disease outcomes, growing evidence highlights the crucial role of the tumor immune microenvironment and its associated gene signatures in shaping prostate cancer biology and progression. To investigate ethnic variations in tumor immune gene signatures, we analyzed transcriptomic data from 35 radical prostatectomy specimens from treatment-naïve patients, including 20 BA and 15 WA men. Gene expression profiles from tumor and adjacent normal tissues were examined using EPIC, xCell, and Ingenuity Pathway Analysis. Differential gene expression was determined by rank testing, and prognostic associations were assessed via univariate Cox regression. WA tumors are enriched for pathways associated with neuroinflammation and oxidative phosphorylation including IL-8 signaling, neuroinflammation, dendritic cell maturation, oxidative phosphorylation, PKCθ signaling in T cells, and NFAT-mediated immune regulation, while PPAR and PD-1/PD-L1 pathways were less active. In contrast, BA tumors are characterized by increased activation of pro-inflammatory and immune-regulatory pathways; display elevated CREB signaling, Th1/Th2 activation, dendritic cell maturation, IL-17 and TREM1 signaling, and IL-17A/F-mediated cytokine production, with reduced activity in PD-1/PD-L1, ILK, IL-3, VEGF, and B-cell receptor pathways. Thirteen immune cell types showed race-specific gene expression patterns including ARG1, FA2H, FBXO39, IGLL3P, KLKB1, MERTK, SEMA3G, and TRPV5 markedly expressed in WA tumors, whereas ARSL, BAALC, CCL23, EPHA2, IGFL2, KRT5, NTM, and NDP upregulated in BA tumors. These results reveal distinct immune-oncological landscapes between BA and WA prostate tumors, highlighting pro-inflammatory pathway enrichment in BA men and underscoring opportunities for ethnicity-specific, genomically informed therapies.
利益披露 Disclosure
S. S. Verma, None..
P. Fu, None..
G. T. MacLennan, None..
L. E. Ponsky, None.