大肠直肠癌中的新陈代谢和线粒体活动之间的异质相互作用
Christophe Desterke1, Yuanji Fu2, Jorge Mata-Garrido2
1Faculty of Medicine, University Paris Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM) Unit UMRS-1310, 94800 Villejuif, France.
Journal of personalized medicine
|December 24, 2025
概括
大肠直肠癌表现出与线粒体活动相关的代谢异质性. 新的R包揭示了瘤亚型的不同代谢概况,有助于个性化癌症治疗的开发.
科学领域:
- 在瘤学瘤学.
- 代谢工程是代谢工程.
- 生物信息学是一种生物信息学.
背景情况:
- 大肠直肠癌 (CRC) 是一种异质恶性瘤,受遗传,环境,营养和生活方式因素的影响.
- 常常CRC的特征是华堡代谢表型,因氧化酸化而增加糖解.
- 了解代谢异质性和线粒体活性对于CRC研究至关重要.
研究的目的:
- 开发和使用R包来探索CRC转录组学数据中的代谢和线粒体活动.
- 研究代谢概况,线粒体功能和CRC亚型之间的关系.
- 在CRC中确定个性化治疗策略的潜在生物标志物.
主要方法:
- 开发两个R包,Keggmetascore和Mitoscore,用于分析KEGG代谢和Mitocarta V3注释.
- 将包装应用于CRC样本中的大量和单细胞RNA测序数据.
- 利用机器学习 (Elastic-net) 进行预测建模和综合多模式数据分析.
主要成果:
- 梅特福林刺激调节了LOVO细胞中的新陈代谢和线粒体活动.
- 单细胞分析显示MSI高瘤中活性化代谢/线粒体,在POLE突变瘤中抑制.
- 大量分析显示,CRC与正常组织中的新陈代谢/线粒体减少;BRAF-V600E突变与抑制的新陈代谢和较少的线粒体相互作用相关.
- 一个新的新陈代谢/线粒体活动评分预测了CMS1-MSI亚型,转移状态和BRAF-V600E突变.
结论:
- 线粒体代谢在结直肠癌亚型化中起着关键作用.
- 代谢和线粒体活动概况作为个性化CRC治疗的有价值的预测生物标志物.
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