食管癌（EC）是一个主要的健康问题，在全球发病率中排名第七，在死亡率中排名第六。尽管多学科治疗方法取得了进步，但 EC 的 5 年生存率仍然很低，仅为 21%。 EC治疗的挑战来自于晚期诊断、高恶性度和不良预后。了解肿瘤微环境至关重要，因为它包括影响肿瘤行为和治疗反应的各种细胞和细胞外成分。肥大细胞（MC）作为组织驻留免疫细胞，在肿瘤动力学中发挥双重作用。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有力的工具，尽管其在EC中的应用有限。在本研究中，我们利用单细胞RNA测序研究了EC的免疫微环境，并建立了全面的免疫微环境。轮廓。我们还对上游转录因子和下游通路富集进行了分析，以进一步全面解读 EC 中的 MC。此外，我们还进行了敲除实验来探索表皮生长因子受体（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。最后，我们构建了 EC 的预后模型，为 EC 的诊断和预后提供了有价值的建议。我们的分析确定了 11 种主要细胞类型，其中 MCs 尤其存在于癌周组织中。对 5,001 个 MC 进行进一步分组，确定了 8 种不同的亚型，包括 SRSF7 高表达的 MC，其表现出强烈的肿瘤偏好和潜在的促肿瘤特性。此外，我们还鉴定了关键信号受体EGFR，并通过体外敲低实验对其进行了验证，证明了其促癌作用。此外，我们建立了一个独立的预后指标，SRSF7 MCs风险评分（SMRS），它显示了高SMRS组与不良预后之间的相关性。这些发现阐明了EC肿瘤微环境内复杂的相互作用，并表明针对特定MCs亚型，特别是通过 EGFR 信号通路，可能会提出新的治疗策略。这项研究建立了一个全面的 EC 免疫图谱，为改进治疗方法提供了见解。版权所有 © 2024 张、张、夏侯、左、薛和张。

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.Copyright © 2024 Zhang, Zhang, Xiahou, Zuo, Xue and Zhang.