通过单细胞RNA测序阐明食管癌肥大细胞的生态景观

食道癌（EC）是一个主要的健康问题，在全球发病率中排名第七，在全球死亡率中排名第六。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，为21％。 EC治疗中的挑战是由于晚期诊断，高恶性肿瘤和预后不良而引起的。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）作为组织居住的免疫细胞在肿瘤动力学中起双重作用。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一种强大的工具，尽管其在EC中的应用受到限制。在这项研究中，我们研究了使用单细胞RNA测序的EC的免疫微环境，并建立了全面的免疫特征。我们还对上游转录因子和下游途径富集进行了分析，以进一步全面地破译EC中的MC。此外，我们进行了敲低实验，以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，从而突出了其作为预后标记的潜力。最后，我们为EC构建了一个预后模型，该模型为EC的诊断和预后提供了有价值的建议。您的分析确定了11种主要细胞类型，其中MC在雌性组织组织组织中特别存在。 5,001个MC的进一步分组确定了8种不同的亚型，包括SRSF7高表达的MC，它们表现出强烈的肿瘤偏好和潜在的肿瘤促进性能。此外，我们确定了关键信号受体EGFR，并通过体外敲低实验证明了其癌症促进作用。此外，我们建立了一个独立的预后指标SRSF7+ MCS风险评分（SMR），该指标显示出高SMRS组与不良预后之间的相关性。这些发现阐明了EC的肿瘤微环境中的复杂相互作用，并建议通过特定的MCS子类型，尤其是通过EGFR Signaling Partitions进行策略，可能是针对特定的MCS子类型的。这项研究建立了一张全面的EC免疫图，为改进的治疗方法提供了见解。

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.