一种新型 M2 样肿瘤相关巨噬细胞相关基因特征,用于预测胃癌的预后和免疫治疗效果。
A novel M2-like tumor associated macrophages-related gene signature for predicting the prognosis and immunotherapy efficacy in gastric cancer.
发表日期:2024 Aug 16
作者:
Xuezhi Li, Xiaodong Qu, Na Wang, Songbo Li, Xingyu Zhao, Kexin Lin, Yongquan Shi
来源:
Cellular & Molecular Immunology
摘要:
M2 样肿瘤相关巨噬细胞(M2 样 TAM)在肿瘤进展和免疫反应中发挥关键作用。然而,M2样TAM相关调控基因在胃癌(GC)中的临床意义和预后价值尚未阐明。在此,我们通过TCGA-STAD和TCGA-STAD的加权基因共表达网络分析鉴定了M2样TAM相关基因。 GSE84437 队列。然后进行 Lasso-Cox 回归分析来筛选特征基因,并构建新的特征来量化每位患者的风险评分。对高危人群的肿瘤突变负荷(TMB)、生存结果、免疫细胞和免疫功能进行分析,以进一步揭示GC患者的免疫状态。使用基因-药物相关性分析和抗癌药物敏感性分析来鉴定潜在的治疗药物。最后,我们通过 qRT-PCR 验证了患者组织中特征基因的 mRNA 表达,并通过 IHC 分析了这些基因的表达分布。开发并验证了 4 个基因(SERPINE1、MATN3、CD36 和 CNTN1)特征,并且风险评分被证明是 GC 患者的独立预后因素。进一步分析发现,高危组GC患者的预后较低危组差,TMB、临床特征、富集通路、TIDE评分、肿瘤微环境特征等方面存在显着差异。最后,我们使用 qRT-PCR 和 IHC 分析来验证特征基因的 mRNA 和蛋白水平表达。这些发现凸显了 M2 样 TAM 的重要性,为 GC 患者的个体化免疫治疗提供了新的视角。© 2024。 )。
M2-like tumor-associated macrophages (M2-like TAMs) play key roles in tumor progression and the immune response. However, the clinical significance and prognostic value of M2-like TAMs-associated regulatory genes in gastric cancer (GC) have not been clarified.Herein, we identified M2-like TAM-related genes by weighted gene coexpression network analysis of TCGA-STAD and GSE84437 cohort. Lasso-Cox regression analyses were then performed to screen for signature genes, and a novel signature was constructed to quantify the risk score for each patient. Tumor mutation burden (TMB), survival outcomes, immune cells, and immune function were analyzed in the risk groups to further reveal the immune status of GC patients. A gene-drug correlation analysis and sensitivity analysis of anticancer drugs were used to identify potential therapeutic agents. Finally, we verified the mRNA expression of signature genes in patient tissues by qRT-PCR, and analyzed the expression distribution of these genes by IHC.A 4-gene (SERPINE1, MATN3, CD36, and CNTN1) signature was developed and validated, and the risk score was shown to be an independent prognostic factor for GC patients. Further analyses revealed that GC patients in the high-risk group had a worse prognosis than those in the low-risk group, with significant differences in TMB, clinical features, enriched pathways, TIDE score, and tumor microenvironment features. Finally, we used qRT-PCR and IHC analysis to verify mRNA and protein level expression of signature genes.These findings highlight the importance of M2-like TAMs, provide a new perspective on individualized immunotherapy for GC patients.© 2024. The Author(s).