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恶性上皮细胞标记驱动的风险特征使食道癌的精确分层成为可能
Hao Zhang1,2, Shizhao Cheng1,2, Yijun Xu1,2
1Tianjin Chest Hospital, Tianjin University, Tianjin, China.
Frontiers in immunology
|June 11, 2025
概括
这项研究揭示了食道状细胞癌 (ESCC) 使用单细胞RNA测序的异质性. 一个新的六基因风险模型预测患者的预后,并指导食道癌的个性化治疗策略.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 生物信息学是一种生物信息学.
背景情况:
- 食道状细胞癌 (ESCC) 是一种异构的癌症,从传统的分期来看,其预后价值有限.
- 内多样性显著影响患者的治疗结果,需要先进的分析方法.
- 单细胞RNA测序 (scRNA-seq) 为瘤细胞性和食道癌的潜在治疗点提供了新的见解.
研究的目的:
- 使用集成的scRNA-seq和大量RNA-seq数据构建食道癌症的全面细胞地图.
- 识别和描述恶性上皮细胞亚群及其调节机制.
- 开发和验证一个多基因风险模型,用于ESCC的预后预测和治疗指南.
主要方法:
- 集成scRNA-seq和大量RNA-seq数据用于细胞地图结构.
- 使用inferCNV用于恶性细胞识别和SCENIC/Monocle用于转录和轨迹分析.
- 使用TCGA和GEO队列开发了一个六基因风险模型,通过qRT-PCR和体外功能测试进行验证.
主要成果:
- 确定了10种细胞类型和6种具有显著异质性的恶性上皮细胞子集群.
- 开发了一个六基因预后模型 (HMGB3,CHORDC1,CTSD,BTG2,MT1E,PHYHD1) 具有高预测总生存率的准确性.
- 风险评分与免疫抑制性瘤微环境和预测的药物敏感性相关;HMGB3敲击抑制了ESCC进展.
结论:
- 在单细胞分辨率下在ESCC中系统地表征上皮质细胞异质性.
- 建立了一个经过验证的风险模型,预测预后,免疫状态和药物反应.
- 强调了HMGB3的致癌作用,并提出了个性化食道癌症治疗的框架.
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