M2 macrophage infiltration drives tumor progression and identifies a multigene prognostic signature in esophageal cancer.

Objective: This study aimed to elucidate the mechanistic role of M2 tumor-associated macrophages in esophageal cancer (EC) progression and to construct an M2 macrophage-related gene signature for prognostic prediction. Methods: Integrated analyses of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data of EC were performed. scRNA-seq data were processed with Seurat and annotated using SingleR. Immune infiltration was evaluated through ssGSEA and CIBERSORT. Weighted gene coexpression network analysis (WGCNA) was used to identify M2 macrophage-associated modules, and candidate genes were intersected with differentially expressed genes (DEGs). Functional enrichment analyses were performed, and a prognostic risk model was established through multivariate Cox regression analysis. The functional roles of key genes were validated through Results: Twelve cell types were identified by scRNA-seq, with macrophages representing the predominant immune population. M2 macrophages formed the major immunosuppressive subtype and were negatively associated with patient survival. WGCNA and DEG analysis identified 25 M2-related genes, from which a four-gene prognostic signature ( Conclusion: A four-gene M2 macrophage-related prognostic model provides reliable prediction of clinical outcomes in EC. Among these genes,