与癌症相关的纤维细胞异质性的治疗影响:从单细胞和多细胞组分析的见解
YuMin Wang1, Yi Ding2, HaoLin Liu3
1Department of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Frontiers in immunology
|July 1, 2025
概括
与癌症相关的纤维细胞 (CAFs) 呈现出各种各样的亚型,这些亚型影响瘤的进展和治疗耐药性. 识别核心CAF基因和开发风险评分模型有助于预测患者的预后,并指导精确的瘤学策略.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 免疫学 免疫学 免疫学
背景情况:
- 癌症相关纤维细胞 (CAF) 是瘤微环境 (TME) 的关键组成部分.
- CAF的异质性显著影响瘤进展,转移和治疗耐药性.
- 在癌症中不同CAF亚群的确切作用仍然不完全理解.
研究的目的:
- 通过单细胞RNA测序 (scRNA-seq) 来研究TME内的CAF异质性.
- 确定CAF亚种群在瘤进展和患者预后中的功能性作用.
- 开发基于CAF相关基因的患者存活率和免疫治疗反应的预测模型.
主要方法:
- scRNA-seq分析以集群CAF亚群并识别关键基因.
- 考克斯和拉索回归用于预后基因选择和风险评分模型开发.
- 为了实验验证,siRNA干扰,qPCR,西式涂抹和药物敏感性测试.
主要成果:
- 确定了四个不同的CAF亚群 (CAF-0,CAF-1,CAF-2,CAF-3) 具有不同的途径活动.
- 一个13核心基因风险评分模型预测高风险患者的存活率和免疫抑制显著降低.
- 像KLRB1和MAP1B这样的核心基因与药物敏感性相关,而HIP1R敲击降低了瘤细胞的表达.
结论:
- 在瘤进展,预后和药物反应中,CAF异质性起着至关重要的作用.
- 开发的风险评分模型为个性化癌症治疗策略提供了基础.
- 这项研究为CAF功能提供了新的见解,并确定了精密瘤学和免疫治疗的潜在治疗点.
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