综合性单细胞转录基因分析揭示了与3p删除相关的瘤微环境和头部和部状细胞癌中的化学抵抗
Xiaochuan Chen1, Siqi Xu1, Junping Pan1
1Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Scientific reports
|March 11, 2025
概括
在头部和部状细胞癌 (HNSCC) 中,染色体3p的删除会产生免疫抑制性瘤微环境 (TME),导致预后不佳,治疗反应减少. 这种遗传变异影响免疫细胞的透,并促进化学抵抗.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 免疫学 免疫学 免疫学
背景情况:
- 头部和部状细胞癌 (HNSCC) 的存活率很低,特别是在局部晚期阶段.
- 染色体3p的删除 (3p删除) 与侵袭性HNSCC和更糟糕的预后有关.
- 瘤微环境 (TME) 极大地影响HNSCC的进展和耐治疗性.
研究的目的:
- 研究3p删除对HNSCC瘤微环境 (TME) 的影响.
- 分析与3p删除相关的免疫细胞透和治疗反应的变化.
- 为了确定HNSCC的潜在治疗点.
主要方法:
- 对单细胞RNA测序 (scRNA-seq) 和批量转录组数据 (TCGA,GEO) 的分析.
- 利用伪时间轨迹,细胞间通信,差异基因表达 (威尔科克森试验) 和预后建模 (LASSO,考克斯回归).
- 评估了免疫细胞透,途径失调 (GSEA),免疫疗法反应 (TIDE) 和SPP1表达.
主要成果:
- 3p删除改变了TME组成,增加了内皮细胞和巨细胞,同时减少了纤维细胞和CD8+ T细胞.
- 在3p删除组中观察到免疫通路 (抗原呈现,T/B细胞信号传递) 的降低调节和增强的葡萄糖分解/脂质代谢.
- 一个预后模型确定了9个与HNSCC存活率差相关的基因;3p删除与存活率差和免疫抑制相关.
- 鉴定出SPP1是与化学抵抗和M2巨分化相关的关键基因.
结论:
- 3p删除显著改变了HNSCC TME,促进了免疫抑制环境,并导致预后不佳.
- 由3p删除形成的遗传和免疫学景观为新型HNSCC疗法提供了潜在的目标.
- 向SPP1和调节免疫抑制TME可能会改善3p删除的HNSCC患者的治疗结果.
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