单细胞RNA测序揭示食管癌中肥大细胞的生态景观

食管癌（EC）是全球发病率第七、死亡率第六的重大健康问题。尽管多学科治疗方法不断进步，但EC的5年生存率仍然较低，仅为21%。EC治疗面临的挑战包括晚期诊断、高恶性程度和预后差。理解肿瘤微环境至关重要，因为它包括多种细胞和细胞外成分，影响肿瘤行为和治疗反应。肥大细胞（MCs）作为组织驻留免疫细胞，在肿瘤动态中具有双重作用。高通量单细胞RNA测序为分析肿瘤异质性和免疫相互作用提供了强大工具，尽管在EC中的应用还有限。本研究利用单细胞RNA测序分析EC的免疫微环境，建立了全面的免疫特征谱。我们还分析了上游转录因子和下游通路富集，深入解析EC中的MCs。此外，我们通过敲除实验探讨了表皮生长因子受体（EGFR）信号通路在MCs-肿瘤细胞相互作用中的作用，强调其作为预后标志物的潜力。最终，我们构建了EC的预后模型，为EC的诊断和预后提供了宝贵的参考。分析显示，在肿瘤周围组织中，MCs尤为丰富。对5001个MCs的进一步分组识别出8个亚型，其中SRSF7高表达的MCs表现出强烈的肿瘤偏好和潜在的促肿瘤特性。此外，识别出关键信号受体EGFR，并通过体外敲除验证其促肿瘤作用。同时建立了独立预后指标——SRSF7+ MCs风险评分（SMRS），高SMRS组与预后差相关。这些发现揭示了EC肿瘤微环境的复杂交互，为靶向特定MC亚型，特别是通过EGFR信号通路，提供了新的治疗策略。本研究建立了EC的全面免疫图谱，为改善治疗方案提供了重要参考。

Esophageal cancer (EC) is a major health issue, ranking seventh in incidence and sixth in mortality worldwide. Despite advancements in multidisciplinary treatment approaches, the 5-year survival rate for EC remains low at 21%. Challenges in EC treatment arise from late-stage diagnosis, high malignancy, and poor prognosis. Understanding the tumor microenvironment is critical, as it includes various cellular and extracellular components that influence tumor behavior and treatment response. Mast cells (MCs), as tissue-resident immune cells, play dual roles in tumor dynamics. High-throughput single-cell RNA sequencing offers a powerful tool for analyzing tumor heterogeneity and immune interactions, although its application in EC is limited.In this study, we investigated the immune microenvironment of EC using single-cell RNA sequencing and established a comprehensive immune profile. We also performed analysis of upstream transcription factors and downstream pathway enrichment to further comprehensively decipher MCs in EC. Besides, we performed knockdown experiments to explore the role of epidermal growth factor receptor (EGFR) signaling pathway in MCs-tumor cell interactions, highlighting its potential as a prognostic marker. Finally, we constructed a prognostic model for EC, which provided valuable suggestions for the diagnosis and prognosis of EC.Our analysis identified 11 major cell types, of which MCs were particularly present in pericarcinoma tissues. Further grouping of the 5,001 MCs identified 8 distinct subtypes, including SRSF7-highly expressed MCs, which showed strong tumor preference and potential tumor-promoting properties. Moreover, we identified the key signaling receptor EGFR and validated it by in vitro knockdown experiments, demonstrating its cancer-promoting effects. In addition, we established an independent prognostic indicator, SRSF7+ MCs risk score (SMRS), which showed a correlation between high SMRS group and poor prognosis.These findings illuminate the complex interactions within the tumor microenvironment of EC and suggest that targeting specific MCs subtypes, particularly via the EGFR signaling pathway, may present novel therapeutic strategies. This study establishes a comprehensive immune map of EC, offering insights for improved treatment approaches.