表观遗传调节,内微生物组和早期结肠直肠癌免疫力
bioRxiv : the preprint server for biology
|April 16, 2025
概括
早发性结肠直肠癌 (CRC) 显示了加速的DNA甲基化衰老. 表观遗传变化,而不是微生物,可能会导致年轻成年人的零星病例,这表明加速衰老在EOCRC发展中的作用.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 结肠直肠癌 (CRC) 发病率在年轻成年人 (<50岁) 中正在上升.
- 大多数早期发病的CRC (EOCRC) 的原因尚不清楚,尽管在约20%的病例中发生了生殖系突变.
- 环境和生活方式等非遗传因素被怀疑是零星EOCRC的贡献者.
研究的目的:
- 调查EOCRC和平均发病CRC (AOCRC) 之间的表观基因组,微生物组和免疫组的差异.
- 为了确定零星EOCRC的潜在病因因素.
主要方法:
- 使用癌症基因组图谱 (TCGA) 数据,比较了EOCRC和AOCRC患者的DNA甲基化模式.
- 在TCGA和两个额外的数据集中识别了瘤内微生物和解化的免疫细胞丰度.
- 使用TCGA和瘤研究信息交换网络 (ORIEN) 的基因表达数据验证的表观遗传发现.
主要成果:
- 与AOCRC患者相比,EOCRC患者的DNA甲基化年龄加速了12年.
- 不同的甲基化位点与CREB信号,G蛋白结合受体信号,细胞形成和S100家族信号相关.
- 在瘤内微生物中没有发现一致的差异,但微生物与免疫系统的相互作用在EOCRC和AOCRC之间有所不同.
结论:
- 表观遗传调节和加速衰老与EOCRC的发展有关.
- 虽然微生物没有一致的差异,但它们的免疫相互作用是不同的,这表明了复杂的相互作用.
- 对表观遗传机制的进一步研究是有必要的,以了解和潜在地治疗EOCRC.
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