剪刀引导的单细胞框架定义了肺腺癌预后和免疫治疗分层的巨噬细胞衍生风险评分
A scissor-guided single-cell framework defines a macrophage-derived risk score for prognostic and immunotherapy stratification in lung adenocarcinoma.
摘要(中文译文)
巨噬细胞是肺腺癌（LUAD）肿瘤微环境中的关键调控者，其功能状态和相互作用模式与预后及免疫治疗反应密切相关。然而，基于单细胞特征衍生的巨噬细胞相关风险模型仍然有限。本研究将GEO单细胞数据集与TCGA-LUAD转录组谱整合，以表征巨噬细胞亚群。应用Scissor方法将临床表型映射至单细胞，并识别表型相关巨噬细胞亚群。利用预后基因构建机器学习模型，命名为Scissor相关巨噬细胞风险评分（SAMRS），并在多个队列中进行评估。进一步纳入基因组特征、免疫治疗反应指标、细胞间通讯、虚拟基因敲除、空间转录组学及功能实验进行机制验证。研究识别出多个功能不同的巨噬细胞亚群，Scissor+巨噬细胞与不良预后及致癌通路活性相关。通讯分析显示巨噬细胞处于中心信号位置。SAMRS模型在多个队列中实现了稳健的预后分层。高SAMRS评分与更高的突变负荷但更强的免疫逃逸信号相关，而低SAMRS评分则显示出更有利的预测免疫治疗反应。模型基因TIMP1在bulk、单细胞和空间分析中表现出一致的信号，功能实验支持其促肿瘤作用。本研究开发了一种单细胞表型引导的巨噬细胞风险评分SAMRS，用于LUAD的预后分层和免疫治疗反应评估。TIMP1相关调控程序可能促进巨噬细胞相关的肿瘤进展。
Abstract
Macrophages are key regulators within the lung adenocarcinoma (LUAD) tumor microenvironment, and their functional states and interaction patterns are closely linked to prognosis and immunotherapy response. However, macrophage-associated risk models derived from single-cell features remain limited. Single-cell datasets from GEO were integrated with TCGA-LUAD transcriptomic profiles to characterize macrophage subpopulations. Scissor was applied to map clinical phenotypes onto single cells and identify phenotype-associated macrophage subsets. Prognostic genes were used to construct a machine learning model termed the Scissor-Associated Macrophage Risk Score (SAMRS), which was evaluated across multiple cohorts. Genomic features, immunotherapy response indicators, cell-cell communication, virtual gene knockout, spatial transcriptomics, and functional experiments were further incorporated for mechanistic validation. Multiple functionally distinct macrophage subsets were identified, and Scissor+ macrophages were associated with poor prognosis and oncogenic pathway activity. Communication analysis placed macrophages at central signaling positions. The SAMRS model achieved robust prognostic stratification across cohorts. High SAMRS scores were linked to higher mutation burden but stronger immune evasion signals, whereas low SAMRS scores showed more favorable predicted immunotherapy response. The model gene TIMP1 demonstrated consistent signals across bulk, single-cell, and spatial analyses, and functional experiments supported its tumor-promoting role. A single-cell phenotype-guided macrophage risk score, SAMRS, was developed for prognostic stratification and immunotherapy response assessment in LUAD. TIMP1-related regulatory programs may contribute to macrophage-associated tumor progression.
如何引用
AMA
Yueyue Shi, Linyue Hai, Guoqing Hou, Zhiqiang Wang, Lanju Wang, Zhenyu Lv, et al. A scissor-guided single-cell framework defines a macrophage-derived risk score for prognostic and immunotherapy stratification in lung adenocarcinoma.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1827555.
APA
Yueyue Shi, Linyue Hai, Guoqing Hou, Zhiqiang Wang, Lanju Wang, Zhenyu Lv, et al (2026). A scissor-guided single-cell framework defines a macrophage-derived risk score for prognostic and immunotherapy stratification in lung adenocarcinoma.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1827555
GB/T 7714
Yueyue Shi, Linyue Hai, Guoqing Hou, Zhiqiang Wang, Lanju Wang, Zhenyu Lv, et al. A scissor-guided single-cell framework defines a macrophage-derived risk score for prognostic and immunotherapy stratification in lung adenocarcinoma.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1827555.
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