肥胖促进了在小鼠和人类结肠瘤中保存的炎症和代谢转录程序
bioRxiv : the preprint server for biology
|July 16, 2025
概括
肥胖会通过改变瘤和脂肪组织中的基因表达来恶化结肠癌,影响炎症和新陈代谢. 这些发现揭示了保存的跨物种机制,将肥胖与结肠癌进展联系起来.
科学领域:
- 在瘤学瘤学.
- 代谢综合征是代谢综合征的一种.
- 基因组学就是基因组学.
背景情况:
- 肥胖是结肠癌的重要危险因素,但潜在的机制尚不清楚.
- 有效的干预措施需要更深入地了解肥胖和结肠癌之间的分子联系.
- 需要新的分子标来打击与肥胖相关的结肠癌患病率的上升.
研究的目的:
- 在结肠瘤和脂肪组织中识别保存的与肥胖相关的转录基因特征.
- 整合来自小鼠模型和人类样本的RNA测序数据,以了解肥胖对结肠癌的影响.
主要方法:
- 使用大肠癌的小鼠模型与 ортотоп瘤器官移植.
- 对来自小鼠瘤和人类结肠瘤/介质脂肪组织的EpCAM阳性细胞进行了转录基因分析.
- 综合了来自ColoCare队列的193个人类结肠瘤和188个人类脂肪样本的数据.
主要成果:
- 在小鼠结肠癌模型中,饮食诱导的肥胖降低了生存率.
- 转录组分析揭示了肥胖驱动的炎症和瘤中的代谢途径丰富.
- 确定了参与先天免疫感应 (例如TLR2,MYD88) 和瘤微环境重塑 (例如MMP9,TGFB1) 的关键基因.
- 肥胖症通过人类样本中的脂肪-瘤受体相互作用放大了炎症信号.
结论:
- 与肥胖相关的脂肪组织功能障碍显著影响跨物种的瘤生物学.
- 一致的跨物种效应突出显示了瘤细胞中保存的炎症和代谢程序.
- 这些发现提供了关于组织间沟通的见解,以及与肥胖相关的结肠癌的潜在治疗点.
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