Zhang Dengfeng, Zhao Fangchao, Liu Haitao, Guo Pengfei, Li Zhirong, Li Shujun
Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
College of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia 010031, China.
Aging (Albany NY). 2024 Jan 25;16(2):1640-1662. doi: 10.18632/aging.205448.
Esophageal cancer is one of the most common malignant tumors with high incidence and mortality rates. Despite the continuous development of treatment options, the prognosis for esophageal cancer patients remains poor. Therefore, there is an urgent need for new diagnostic and therapeutic targets in clinical practice to improve the survival of patients with esophageal cancer.
In this study, we conducted a comprehensive scRNA-seq analysis of the tumor microenvironment in primary esophageal tumors to elucidate cell composition and heterogeneity. Using Seurat, we identified eight clusters, encompassing non-immune cells (fibroblasts, myofibroblasts, endothelial cells, and epithelial cells) and immunocytes (myeloid-derived cells, T cells, B cells, and plasma cells). Compared to normal tissues, tumors exhibited an increased proportion of epithelial cells and alterations in immune cell infiltration. Analysis of epithelial cells revealed a cluster (cluster 0) with a high differentiation score and early distribution, suggesting its importance as a precursor cell.
Cluster 0 was characterized by high expression of FABP6, indicating a potential role in fatty acid metabolism and tumor growth. T cell analysis revealed shifts in the balance between Treg and CD8+ effector T cells in tumor tissues. Cellular communication analysis identified increased interactions between FABP6+ tumor cells and T cells, with the involvement of the MIF-related pathway and the CD74-CD44 interaction. This study provides insights into the cellular landscape and immune interactions within esophageal tumors, contributing to a better understanding of tumor heterogeneity and potential therapeutic targets.
食管癌是最常见的恶性肿瘤之一，发病率和死亡率都很高。尽管治疗方案不断发展，但食管癌患者的预后仍然很差。因此，临床实践中迫切需要新的诊断和治疗靶点，以提高食管癌患者的生存率。
在本研究中，我们对原发性食管肿瘤的肿瘤微环境进行了全面的单细胞RNA测序（scRNA-seq）分析，以阐明细胞组成和异质性。使用Seurat软件，我们识别出八个细胞簇，包括非免疫细胞（成纤维细胞、肌成纤维细胞、内皮细胞和上皮细胞）和免疫细胞（髓系来源细胞、T细胞、B细胞和浆细胞）。与正常组织相比，肿瘤中上皮细胞比例增加，免疫细胞浸润也发生了改变。对上皮细胞的分析发现了一个具有高分化评分和早期分布的细胞簇（细胞簇0），表明其作为前体细胞的重要性。
细胞簇0的特征是FABP6高表达，表明其在脂肪酸代谢和肿瘤生长中可能发挥作用。T细胞分析显示肿瘤组织中调节性T细胞（Treg）和CD8+效应T细胞之间的平衡发生了变化。细胞间通讯分析确定了FABP6+肿瘤细胞与T细胞之间的相互作用增加，涉及巨噬细胞移动抑制因子（MIF）相关途径和CD74-CD44相互作用。本研究为食管肿瘤内的细胞格局和免疫相互作用提供了见解，有助于更好地理解肿瘤异质性和潜在的治疗靶点。
