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| The effect of MAGEA3 gene expression on the immune microenvironment of Asian patients with gastric cancer |
| JIN Jinji, CAI Yiqi, YANG Jiaxin, CHENG Jun, WANG Pengfei |
| Departments of GastrointestinalSurgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China |
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| Cite this article: |
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JIN Jinji,CAI Yiqi,YANG Jiaxin, et al. The effect of MAGEA3 gene expression on the immune microenvironment of Asian patients with gastric cancer[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(11): 896-904.
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Abstract Objective: To reveal the impact of MAGEA3 on the immune microenvironment of Asian gastric cancer patients through bioinformatic analysis of the gastric cancer dataset from The Asian Cancer Research Group (ACRG) for validation with clinical serum samples collected from gastric cancer patients. Methods:Altogether 300 gastric cancer patients in the ACRG GSE52254 dataset were divided as MAGEA3 high expression group and low expression group based on the median expression value. The ESTIMATE and CIBERSORT methods were then used to calculate the immune and stromal components as well as the proportions of 22 infiltrating lymphocyte subsets in both groups. The differences in immune microenvironment and immune cells between the two groups were compared, and further GSEA analysis was conducted to determine the changes in related pathways by MAGEA3. Serum samples of 86 gastric cancer patients admitted to the First Affiliated Hospital of Wenzhou Medical University from January to April 2022 were collected to detect the expression levels of MAGEA3 protein and the correlation between MAGEA3 protein and subpopulations of peripheral blood lymphocytes was verified through ELISA and flow cytometry. Results: The ESTIMATE results showed that theimmune scores and stromal scores of the MAGEA3 high expression group were significantly lower than those of the MAGEA3 low expression group (P<0.001), and Spearman analysis revealed a negative correlation between MAGEA3 expression and immune scores (r=-0.244, P<0.001) and stromal scores (r=-0.266, P<0.001). Further GSEA analysis suggested that there were pathways related to T cell activation, proliferation, macrophage activation, and immune cell regulation enriched in the MAGEA3 low expression group. The CIBERSORT results showed that in the MAGEA3 low expression group, there was more infiltration of naive B cells, plasma cells, CD8+ T cells, γδT cells, and activated NK cells, and less infiltration of macrophages M0. Clinical serum samples showed that MAGEA3 expression had significant negative correlation with CD8+ T cells (r=-0.310, P=0.004),which was consistent with the ACRG data analysis. Conclusion: The expression level of MAGEA3 may affect the immune components of the immune microenvironment of gastric cancer, revealing its potential as a target for immunotherapy and a biological marker
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Received: 05 May 2023
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