Li Xuezhi, Qu Xiaodong, Wang Na, Li Songbo, Zhao Xingyu, Lin Kexin, Shi Yongquan
State key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
Discov Oncol. 2024 Aug 16;15(1):353. doi: 10.1007/s12672-024-01221-8.
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.
M2样肿瘤相关巨噬细胞（M2样TAMs）在肿瘤进展和免疫反应中起关键作用。然而，M2样TAMs相关调控基因在胃癌（GC）中的临床意义和预后价值尚未明确。
在此，我们通过对TCGA-STAD和GSE84437队列进行加权基因共表达网络分析，鉴定出M2样TAM相关基因。然后进行Lasso-Cox回归分析以筛选特征基因，并构建一个新的特征来量化每位患者的风险评分。对风险组中的肿瘤突变负担（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。通过基因-药物相关性分析和抗癌药物敏感性分析来确定潜在的治疗药物。最后，我们通过qRT-PCR验证患者组织中特征基因的mRNA表达，并通过免疫组化分析这些基因的表达分布。
开发并验证了一个由4个基因（SERPINE1、MATN3、CD36和CNTN1）组成的特征，风险评分被证明是GC患者的独立预后因素。进一步分析显示，高风险组的GC患者预后比低风险组更差，在TMB、临床特征、富集通路、TIDE评分和肿瘤微环境特征方面存在显著差异。最后，我们使用qRT-PCR和免疫组化分析验证了特征基因的mRNA和蛋白水平表达。
这些发现突出了M2样TAMs的重要性，为GC患者的个体化免疫治疗提供了新的视角。
