TNFSF15 and MIA Variant Associated with Immunotherapy and Prognostic Evaluation in Esophageal Cancer

Jun You; Jiaojiao Bian; Jian Chen; Tianqin Xia; Ailu Deng; Ming Zhang; YiChen Liao; Huling Wen; Zhengmin Xu

doi:10.1155/2023/1248024

TNFSF15 and MIA Variant Associated with Immunotherapy and Prognostic Evaluation in Esophageal Cancer

J Oncol. 2023 Mar 10:2023:1248024. doi: 10.1155/2023/1248024. eCollection 2023.

Authors

Jun You^{1

2}, Jiaojiao Bian¹, Jian Chen³, Tianqin Xia¹, Ailu Deng¹, Ming Zhang⁴, YiChen Liao¹, Huling Wen⁵, Zhengmin Xu¹

Affiliations

¹ 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.
² People's Hospital of Leshan, Leshan 614000, Sichuan, China.
³ Department of Thoracic Surgery, Rheumatic Hematology Department, Nuclear Medicine Infectious Diseases, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan, China.
⁴ Nanchong Hospital of Traditional Chinese Medicine, Nanchong 637000, Sichuan, China.
⁵ Cancer Hospital, Affiliated to Medical College of Shantou University, Shantou 515041, China.

Abstract

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 (P < 0.05). The risk assessment analysis also showed that tumor stage was positively correlated with tumor risk in ESCA (P < 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 (P < 0.05). In contrast, their expressions were decreased in high differentiated tissues (P < 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.

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.