Wang Bolin, Zhou Xiaofeng, Wu Di, Gao Lu, Wan Zhihua, Wu Ruifeng
Graduate School of Chengde Medical College, Chengde, Hebei, China.
Department of Chest Surgery, Baoding First Central Hospital, Baoding, Hebei, China.
Discov Oncol. 2025 Mar 18;16(1):352. doi: 10.1007/s12672-025-02123-z.
This study aimed to investigate the correlation between M2 macrophages activity with the prognosis of lung adenocarcinoma (LUAD). We sought to identify key genes associated with M2 macrophage activity and examine their relationship with clinicopathological features to elucidate the underlying mechanism.
Published datases were analyzed for differentially expressed genes. After quality control, batch effect removal, and annotation, the scRNA dataset identified M2 macrophage-associated differentially expressed genes in the LUAD group, which were cross-analyzed and referred to as M2 macrophage-linked genes. A risk model was generated using machine learing for these genes. Thereafter, two bulk RNA-seq datasets were used to evaluate the model. We computed risk scores for all samples and grouped them into low and high risk, aiding in the comparison of clinical characteristics, immune and stromal infiltration, and drug sensitivity. Finally, key genes were validated through immunohistochemistry in IPA samples.
We identified four key M2 macrophage-linked genes: TIMP1, CAV2, MIF, and SELENBP1. Survival durations in the high-riskscore cluster were lower across the TCGA-LUAD (P = 1.2 × 10), GSE14814 (P = 0.02), and GSE37745 (P = 0.01) data sets. The stromal score, fibroblast infiltration, and cytokinesis activation were increased in the high-risk subgroup. Neutrophil and endothelial cell infiltration and activation of the linolenic acid pathway occurred in the low-risk group. IHC confirmed that CAV2 and SELENBP1 expression was significantly reduced, while TIMP1 and MIF were significantly increased in LUAD, which was consistent with the bioinformatics findings.
The role of M2 macrophages in tumor progression could anticipate the prognosis of LUAD and develop novel immunotherapy strategies.
本研究旨在探讨M2巨噬细胞活性与肺腺癌（LUAD）预后之间的相关性。我们试图鉴定与M2巨噬细胞活性相关的关键基因，并研究它们与临床病理特征的关系，以阐明潜在机制。
对已发表的数据集进行差异表达基因分析。经过质量控制、批次效应消除和注释后，单细胞RNA测序（scRNA）数据集确定了LUAD组中与M2巨噬细胞相关的差异表达基因，对其进行交叉分析并称为M2巨噬细胞相关基因。使用机器学习为这些基因生成风险模型。此后，使用两个批量RNA测序数据集评估该模型。我们计算了所有样本的风险评分，并将其分为低风险和高风险，以比较临床特征、免疫和基质浸润以及药物敏感性。最后，通过免疫组织化学在独立患者队列（IPA）样本中验证关键基因。
我们鉴定出四个关键的M2巨噬细胞相关基因：金属蛋白酶组织抑制因子1（TIMP1）、小窝蛋白2（CAV2）、巨噬细胞迁移抑制因子（MIF）和硒结合蛋白1（SELENBP1）。在TCGA-LUAD（P = 1.2×10）、GSE14814（P = 0.02）和GSE37745（P = 0.01）数据集中，高风险评分组的生存时间较短。高风险亚组的基质评分、成纤维细胞浸润和细胞分裂激活增加。低风险组发生中性粒细胞和内皮细胞浸润以及亚麻酸途径激活。免疫组织化学证实，LUAD中CAV2和SELENBP1表达显著降低，而TIMP1和MIF显著增加，这与生物信息学结果一致。
M2巨噬细胞在肿瘤进展中的作用可以预测LUAD的预后并制定新的免疫治疗策略。
