单细胞和转录基因分析显示,阻塞性睡眠呼吸暂停 (OSA) 与肺癌相关的干细胞驱动的免疫逃避
Yu-Wei Liu1, Chi-Jen Wu2,3, Kai-Fu Chang4,5
1Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
Journal of Cancer
|January 26, 2026
概括
阻塞性睡眠呼吸暂停 (OSA) 和间歇性缺氧 (IH) 与肺癌发育,免疫抑制和不良结果有关. 一个六基因签名预测预后,并确定潜在的治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 睡眠医学 睡眠医学
背景情况:
- 阻塞性睡眠呼吸暂停 (OSA) 涉及反复的间歇性缺氧 (IH),与肺癌发病率和死亡率越来越相关.
- 肺癌中IH,免疫重塑,干性和治疗抵抗之间的关系需要进一步阐明.
研究的目的:
- 研究IH对免疫细胞群和肺癌中转录模式的影响.
- 评估瘤干和免疫检查点表达,治疗耐药性和患者预后之间的关联.
- 开发和验证肺癌的根基基因预后基因签名.
主要方法:
- 综合单细胞RNA测序IH暴露的小鼠肺组织与TCGA-LUAD和GSE31210队列的大量转录组数据.
- 使用CytoTRACE和基于转录基因组的评分量化茎度.
- 评估了与免疫透,免疫检查点,TIDE分数,药物敏感性和免疫治疗反应的关联.
- 使用 LASSO 考克斯回归构建并验证了一个预后模型.
主要成果:
- IH诱导了显著的免疫重塑,包括效应性T细胞和单细胞/巨细胞的扩张,减少了B细胞和树突细胞.
- 高干度瘤表现出线粒体/代谢应激特征,增加免疫检查点基因表达 (PD-1,PD-L1,CTLA4,LAG3) 和更高的TIDE分数.
- 升高的茎度与较差的存活率和免疫治疗反应的减少相关.
- 六个基因的干性特征 (EIF5A,MELTF,SEMA3C,CPS1,TCN1,SELENOK) 稳定地将患者分为高风险和低风险组.
结论:
- 与OSA相关的IH促进了干性,免疫抑制和肺癌的不良结果.
- 识别的茎状特征可以作为预后生物标志物.
- 向干部和免疫检查点可能会提高OSA相关肺癌的免疫疗法疗效.
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