Aims: The aim of the present study was to investigate the relationship between the cellular ecosystem and the progression of esophageal carcinoma (ESCA) based on the evolution of macrophages and to analyze the potential of using macrophages as a new therapeutic approach in ESCA treatment. Background: Macrophage-based immunotherapy could be used for treating ESCA patients, but its clinical application is limited by the intra-tumor heterogeneity of macrophages. Objective: The objective of this study was to analyze the diversity, differentiation trajectory, and intercellular communication of macrophages in ESCA and its prognostic significance. Methods: Single-cell RNA sequencing (scRNA-seq) data in the GSE154763 dataset were downloaded from Gene Expression Omnibus (GEO) to identify cell clusters and annotate cell types using the Seurat R package. The scRNA-seq profiles of macrophages were extracted, and cluster analysis was performed to identify macrophage subsets. The differentiation trajectories of macrophage subgroups were visualized employing Monocle2. Finally, ligand-receptor pairs and communication intensity among the classified subgroups were analyzed using CellChat. Results: A total of 8 cell types were identified between ESCA tissues and paracancer tissues. The most abundant macrophages in ESCA tissues were further divided into 5 cell clusters. Compared with the normal tissues, the proportion of HSPA6+ macrophages in ESCA tissues increased the most, and the number of ligand-receptor pairs that mediated the communication of HSPA6+ macrophages with mast cells and monocytes also increased significantly. More importantly, a high proportion of HSPA6+ macrophages was inversely correlated with the survival outcomes for ESCA patients. Conclusions: This study analyzed the diversity, distribution and differentiation trajectory of macrophages in ESCA tissues at single-cell level and classified a prognostic macrophage subtype (HSPA6+ macrophages) of ESCA, providing a theoretical basis for macrophage-targeted therapy in ESCA.

中文翻译：

---

人类食管癌预后巨噬细胞亚群的鉴定和表征

目的：本研究的目的是基于巨噬细胞的进化来研究细胞生态系统与食管癌（ESCA）进展之间的关系，并分析使用巨噬细胞作为 ESCA 治疗新治疗方法的潜力。背景：基于巨噬细胞的免疫疗法可用于治疗ESCA患者，但其临床应用受到巨噬细胞肿瘤内异质性的限制。目的：本研究的目的是分析 ESCA 中巨噬细胞的多样性、分化轨迹和细胞间通讯及其预后意义。方法：从 Gene Expression Omnibus (GEO) 下载 GSE154763 数据集中的单细胞 RNA 测序 (scRNA-seq) 数据，以使用 Seurat R 包识别细胞簇并注释细胞类型。提取巨噬细胞的 scRNA-seq 谱，并进行聚类分析以鉴定巨噬细胞亚群。使用 Monocle2 可视化巨噬细胞亚群的分化轨迹。最后，使用 CellChat 分析了分类亚组之间的配体-受体对和通讯强度。结果：ESCA组织和癌旁组织中总共鉴定出8种细胞类型。ESCA组织中最丰富的巨噬细胞进一步分为5个细胞簇。与正常组织相比，ESCA组织中HSPA6+巨噬细胞的比例增加最多，介导HSPA6+巨噬细胞与肥大细胞和单核细胞通讯的配体受体对数量也显着增加。更重要的是，高比例的 HSPA6+ 巨噬细胞与 ESCA 患者的生存结果呈负相关。结论：本研究在单细胞水平分析了ESCA组织中巨噬细胞的多样性、分布和分化轨迹，并对ESCA的预后巨噬细胞亚型（HSPA6+巨噬细胞）进行了分类，为ESCA的巨噬细胞靶向治疗提供了理论依据。