Background. Esophageal cancer (ESCA) is a common gastrointestinal tumor, and China is one of the regions with a high incidence. Tumor immune-related cells play important roles in the tumorigenesis and development of ESCA. However, the role of tumor immune-related genes in the development of ESCA has not been established. Methods. In this study, weighted gene coexpression network analysis (WGCNA) was used to analyze ESCA gene expression using data from The Cancer Genome Atlas (TCGA) database. Gene expression was associated with clinical traits, and modules related to CD8+T cells, dendritic cells, and regulatory T cells (Tregs) were obtained. Results. The GO analysis showed that inflammatory chemotaxis networks were activated by cell chemotaxis, chemokine activity, and chemokine binding receptor. Three hub genes (IL17C, TNFSF15, and MIA) related to tumor immunity and metastasis were identified by WGCNA, and the abnormal expression of each hub gene in ESCA has a poor prognosis, especially in patients with high expression (). The risk assessment analysis also showed that tumor stage was positively correlated with tumor risk in ESCA (). Therefore, more than 50 pairs of tumor tissues from the T1–T3 stages with different degrees of differentiation and paracancerous tissues were selected to confirm the expression of the three genes using RT-qPCR and immunofluorescence (IF). The infiltration of CD8+ T cells in tumor tissues was lower than that in normal tissues. According to the RT-qPCR, the expressions of IL17 C, TNFSF15, and MIA in moderately and poorly differentiated tissues were significantly higher than those in normal tissues (). In contrast, their expressions were decreased in high differentiated tissues (). Furthermore, IL17C, TNFSF15, and MIA were all positively correlated with immune checkpoint PD-1; TNFSF15 and MIA were also positively correlated with CTLA4, TIGIT, and CD96. Conclusion. In summary, IL17C, TNFSF15, and MIA may act as biomarkers for prognosis in moderately and poorly differentiated ESCAs, and they may be used as predictive genes of immunotherapy associated with CD8+ T cell and Tregs invasion in ESCAs.

中文翻译：

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TNFSF15 和 MIA 变异与食管癌的免疫治疗和预后评估相关

背景。食管癌（ESCA）是一种常见的消化道肿瘤，我国是高发地区之一。肿瘤免疫相关细胞在ESCA的发生发展过程中起重要作用。然而，肿瘤免疫相关基因在 ESCA 发展中的作用尚未确定。方法。在这项研究中，加权基因共表达网络分析 (WGCNA) 用于使用来自癌症基因组图谱 (TCGA) 数据库的数据分析 ESCA 基因表达。基因表达与临床特征相关，并获得了与 CD8+T 细胞、树突状细胞和调节性 T 细胞 (Treg) 相关的模块。结果. GO 分析显示炎症趋化网络被细胞趋化、趋化因子活性和趋化因子结合受体激活。WGCNA鉴定出3个与肿瘤免疫和转移相关的hub基因（IL17C、TNFSF15和MIA），ESCA中各hub基因异常表达预后较差，尤其是高表达患者。). 风险评估分析还显示，肿瘤分期与ESCA肿瘤风险呈正相关（). 因此，选择了 50 多对来自不同分化程度的 T1-T3 期肿瘤组织和癌旁组织，使用 RT-qPCR 和免疫荧光 (IF) 来确认这三个基因的表达。CD8+T细胞在肿瘤组织中的浸润低于正常组织。RT-qPCR显示，IL17C、TNFSF15、MIA在中低分化组织中的表达明显高于正常组织（). 相反，它们在高分化组织中的表达降低（). 此外，IL17C、TNFSF15、MIA均与免疫检查点PD-1呈正相关；TNFSF15 和 MIA 也与 CTLA4、TIGIT 和 CD96 呈正相关。结论。总之，IL17C、TNFSF15 和 MIA 可作为中分化和低分化 ESCA 预后的生物标志物，它们可作为与 ESCA 中 CD8+ T 细胞和 Treg 侵袭相关的免疫治疗的预测基因。