Ezrin's role in gastric cancer progression: Implications for immune microenvironment modulation and therapeutic potential

• Published in: Heliyon Vol. 10; no. 5; p. e27155
• Main Authors: Zhu, Yanli, Zhang, Xue, Chen, Yi, Liu, Qianli, Yang, Jin, Fan, Xiaoxiao, Song, Hanjun, Cheng, Zhuoxin, Liu, Shuang
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.03.2024; Elsevier
• Subjects: Epithelial-mesenchymal transformation; Ezrin; Gastric cancer; Immune microenvironment modulation; Metastatic regulation; Metastatic regulation; Immune microenvironment modulation; Epithelial-mesenchymal transformation; Gastric cancer; Ezrin
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e27155

At present, surgical resection is the most effective method for the treatment of gastric cancer. However, death caused by inoperable metastasis is still very common, despite research in this area. The mechanisms underlying the occurrence, development, and metastasis of gastric cancer are not fully understood. Ezrin, a plasma membrane-microfilament junction participates in a variety of cellular activities and is closely related to tumorigenesis and development. Few studies have explored the relationship between the tumor immune microenvironment and ezrin expression in gastric cancer. In this study, we used proteomic techniques to analyze the differentially expressed proteins between the gastric cancer cell lines MKN-45 and HGC-27 and screened ezrin as the target protein. We collected patient information from The TCGA and GEO databases, and the results showed that ezrin was positively correlated with adverse clinical features. We further explored the relationship between ezrin expression levels, immune microenvironment, and genomic changes. We found that ezrin was involved in immune regulation and genomic instability in gastric cancer. When the expression of ezrin is high, immune cell infiltration also increases. We also predicted that ezrin is closely related to immunotherapy and chemosensitivity. Single-cell transcriptome data showed that the ezrin gene was mainly expressed in B cells and epithelial cells, and the expression of EZR in these epithelial cells was positively correlated with the epithelial-mesenchymal transformation pathway and Pi3k-AKT pathway score. Through functional verification of the stably transfected cell line constructed by lentivirus, the results of the liver metastasis model in nude mice suggested that high expression of ezrin leads to the formation of more metastatic foci. In summary, our results clarify the prognostic, immunological, and therapeutic value of ezrin in gastric cancer and provide a theoretical basis for more accurate treatment.