原发性结肠癌通过抑制线粒体综合体I活动,损害肌肉能量代谢
Xiaolin Li1, Miranda van der Ende1,2, Hanneke Moonen1,3
1Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands.
Journal of cachexia, sarcopenia and muscle
|November 12, 2025
概括
结肠癌在疾病早期通过损害线粒体功能而导致肌肉损失. 这种功能障碍,特别是复杂I减小,在临床缓解症之前,为早期干预提供了潜在的目标.
科学领域:
- 线粒体生物学 线粒体生物学
- 在瘤学瘤学.
- 肌肉生理学 肌肉生理学
背景情况:
- 结肠癌 (CC) 是全球癌症死亡的主要原因.
- 肌肉消耗的特征是白内障,影响30%的CC患者,影响治疗结果和存活率.
- 在CC中早期肌肉功能障碍的机制仍然不太清楚,需要对代谢变化的研究.
研究的目的:
- 为了研究结肠癌不同阶段的骨肌肉中的线粒体功能.
- 在结肠癌中识别与肌肉功能障碍相关的早期代谢变化.
- 探索线粒体变化与缓解症的出现之间的关系.
主要方法:
- 分析了来自原发性CC,转移性CC和年龄匹配的对照患者的直腹肌活检.
- 使用高分辨率呼吸计评估线粒体的氧气消耗.
- 通过RNA测序评估与氧化酸化相关的基因表达特征.
主要成果:
- 初级CC患者的复合I活性降低,氧化酸化基因的补偿上调.
- 肝转移患者在没有补偿基因上调的情况下表现出更严重的线粒体功能障碍 (复合I和II减少).
- 在身体功能或全身炎症标志物显著下降之前检测到线粒体功能障碍.
结论:
- 结肠癌与骨肌中的特定阶段的线粒体功能障碍有关.
- 早期的复杂I损伤和转录适应发生在初级CC中,临床缓解症之前.
- 线粒体功能障碍可以作为癌症引起的肌肉损失的早期生物标志物和治疗点.
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