GIMAP1 interacts with TMX1 to improve lung adenocarcinoma prognosis by influencing tumor immune microenvironment

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2025-01, Vol.1871 (3), p.167661, Article 167661
• Main Authors: Ruan, Pinglang, Li, Jiani, Abdelhalim, Khalid A., Tang, Zhongxiang, Tan, Weitong, Yao, Jiaoyang, Tan, Yurong, Wang, Lili
• Format: Article
• Language: English
• Subjects: GIMAPs. TMX1; Lung cancer; Tumor microenvironment
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2025.167661

Recent studies have indicated that the GIMAP family is downregulated in lung cancer and correlates with poor prognosis, although the underlying mechanisms remain unclear. This study aimed to elucidate the mechanism behind GIMAP1 downregulation in lung cancer. Bioinformatics tools were employed to assess the correlation between the GIMAP family and various cancers. Specifically, GIMAP1 was selected for further investigation, and its role in lung adenocarcinoma was confirmed through RNA sequencing analysis, Gene Set Enrichment Analysis (GSEA) of differentially expressed genes, correlation analysis with immune cell infiltration, and assay of the GIMAP1-TMX1 interaction. Based on bioinformatics analysis and real-world cohort studies, it was found that GIMAP1 was underexpressed in lung cancer tissues but exhibited elevated expression following immunotherapy. Overexpression of GIMAP1 was shown to influence several immune signaling pathways. In patients with high GIMAP1 expression, there was a significant increase in the infiltration of CD8+ T cells, activated memory CD4+ T cells, monocytes, and M1 macrophages; conversely, infiltration by M0 macrophages, resting dendritic cells (DCs), and plasma cells was significantly reduced. In vitro experiments showed that high levels of GIMAP1 increased the percentage of Treg, NK, and NKT cells. Additionally, GIMAP1 directly interacted with TMX1 and modulated the expression of downstream immune-related genes including CMTM5, IL17F, TRAV34, and XCR1. Therefore, GIMAP1 may serve as a promising therapeutic target in lung cancer, influencing both disease initiation and progression. [Display omitted] •GIMAP1 is downregulated in lung cancer and GIMAP1 downregulation is correlated with poor prognosis.•A prognostic risk model showed that GIMAP1-induced CMTM5, IL17F, TRAV34, and XCR1 expression are associated with improved survival.•GIMAP1 enhances the expression of CMTM5, IL17F, TRAV34, and XCR1 via interaction with TMX1.