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

Yanli Zhu; Xue Zhang; Yi Chen; Qianli Liu; Jin Yang; Xiaoxiao Fan; Hanjun Song; Zhuoxin Cheng; Shuang Liu

doi:10.1016/j.heliyon.2024.e27155

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

Heliyon. 2024 Feb 28;10(5):e27155. doi: 10.1016/j.heliyon.2024.e27155. eCollection 2024 Mar 15.

Authors

Yanli Zhu^{1

2

3}, Xue Zhang^{1

2}, Yi Chen¹, Qianli Liu¹, Jin Yang^{1

2}, Xiaoxiao Fan^{1

2}, Hanjun Song^{1

2}, Zhuoxin Cheng⁴, Shuang Liu^{1

2}

Affiliations

¹ Jiamusi University School of Basic Medicine, Jiamusi 154007, China.
² Key Laboratory of Microecology-immune Regulatory Network and Related Diseases, Jiamusi 154007, China.
³ Digestive Disease Center, The First Affiliated Hospital of Jiamusi University, Heilongjiang Province, Jiamusi 154000, China.
⁴ Department of General Surgery, The First Affiliated Hospital of Jiamusi University, Heilongjiang Province, Jiamusi 154000, China.

Abstract

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.

Keywords: Epithelial-mesenchymal transformation; Ezrin; Gastric cancer; Immune microenvironment modulation; Metastatic regulation.