You Jun, Bian Jiaojiao, Chen Jian, Xia Tianqin, Deng Ailu, Zhang Ming, Liao YiChen, Wen Huling, Xu Zhengmin
Institute of Medicine, School of Pharmacy, Rheumatic Hematology Department of Affiliated Hospital, Translational Medicine Research Center, Institute of Hepatobiliary Research, North Sichuan Medical College, Nanchong 637000, Sichuan, China.
People's Hospital of Leshan, Leshan 614000, Sichuan, China.
J Oncol. 2023 Mar 10;2023:1248024. doi: 10.1155/2023/1248024. eCollection 2023.
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.
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.
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 ( < 0.05). The risk assessment analysis also showed that tumor stage was positively correlated with tumor risk in ESCA ( < 0.05). 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 ( < 0.05). In contrast, their expressions were decreased in high differentiated tissues ( < 0.05). 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.
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.
食管癌（ESCA）是一种常见的胃肠道肿瘤，中国是高发地区之一。肿瘤免疫相关细胞在ESCA的发生发展中起重要作用。然而，肿瘤免疫相关基因在ESCA发展中的作用尚未明确。
在本研究中，使用加权基因共表达网络分析（WGCNA），利用来自癌症基因组图谱（TCGA）数据库的数据来分析ESCA基因表达。将基因表达与临床特征相关联，获得了与CD8 + T细胞、树突状细胞和调节性T细胞（Tregs）相关的模块。
基因本体（GO）分析表明，炎症趋化网络通过细胞趋化、趋化因子活性和趋化因子结合受体被激活。通过WGCNA鉴定出三个与肿瘤免疫和转移相关的枢纽基因（IL17C、TNFSF15和MIA），每个枢纽基因在ESCA中的异常表达预后较差，尤其是高表达患者（<0.05）。风险评估分析还表明，肿瘤分期与ESCA中的肿瘤风险呈正相关（<0.05）。因此，选择50多对不同分化程度的T1 - T3期肿瘤组织和癌旁组织，使用逆转录定量聚合酶链反应（RT - qPCR）和免疫荧光（IF）来确认这三个基因的表达。肿瘤组织中CD8 + T细胞的浸润低于正常组织。根据RT - qPCR，IL17C、TNFSF15和MIA在中低分化组织中的表达明显高于正常组织（<0.05）。相反，它们在高分化组织中的表达降低（<0.05）。此外，IL17C、TNFSF15和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。
总之，IL17C、TNFSF15和MIA可能作为中低分化ESCA预后的生物标志物，并且它们可能用作与ESCA中CD8 + T细胞和Tregs浸润相关的免疫治疗的预测基因。
