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编码免疫反应多个调节器的基因在非裔美国人的前列腺瘤微环境中被甲基化

Vinay Kumar¹, Tara Sinta Kartika Jennings¹, Lucas Ueta¹

¹Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA.

|July 29, 2025

概括

患有前列腺癌的非裔美国男性在瘤相邻的肌层中显示出明显的DNA甲基化模式,全球甲基化水平较高与晚期疾病有关. 针对这些表观遗传变化可能有助于减少前列腺癌差异.

科学领域:

表观遗传学和癌症生物学
基因组医学是基因组医学.
健康差距研究研究研究研究

背景情况:

前列腺癌 (PCa) 不成比例地影响非裔美国人 (AA) 的男性,在较年轻的年龄呈现,晚期,与欧洲美国人 (EA) 的男性相比,结果更差.
瘤邻性肌瘤 (TAS) 在癌症进展中起着关键作用,其表观遗传变化,特别是DNA甲基化,与PCa差异有关.

研究的目的:

研究非洲裔美国人 (AA) 和欧洲裔美国人 (EA) 前列腺癌 (PCa) 患者之间瘤相邻肌层 (TAS) 中的DNA甲基化概况的差异.
探索利用脱甲基化剂向树皮DNA甲基化的潜力,作为解决PCa健康差异的治疗策略.

主要方法:

甲基结合域测序 (MBD-seq) 和长间隔核元素-1 (LINE-1) 试验被用于分析AA (n=17) 和EA (n=15) PCa患者TAS中的DNA甲基化.
对差异甲基化基因进行了途径分析. 在初级培养的AA和EA癌相关纤维细胞 (CAFs) 中的DNA甲基化与TAS进行了比较,CAFs用5-阿扎西丁 (5-AzaC) 治疗.

主要成果:

AA TAS的全球DNA甲基化水平明显高于EA TAS (p < 0.001).
在3268个差异甲基化区域 (DMR) 中,85%显示AA TAS甲基化增加,影响了1648个基因. 根据甲基化水平确定了两个AA亚组,较高的甲基化与较高的格里森得分相关.
途径分析显示,在免疫反应,Wnt/β-catenin,androgen和其他关键信号通路中,AA TAS中甲基化基因的丰富. 在AA CAF和TAS中确定了协同甲基化的基因,5-AzaC治疗减少了AA CAF中的DNA甲基化.

结论:

在患有前列腺癌的非洲裔美国男性中观察到一种明显的 stromal methylome,其特征是DNA甲基化增加.
这些发现为开发针对瘤微环境的新型治疗策略提供了基础,可能包括去甲基化剂,以解决AA男性前列腺癌差异.

关键词:

非洲裔美国人.通过DNA甲基化.欧洲人美国人美国人前列腺癌是前列腺癌.瘤微环境是一个微环境.

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