IFI30 Modulates Immune Microenvironment And Improves Prognosis In Glioblastoma

Abstract

Abstract Background Immunotherapy has brought new hope as a potentially effective treatment for Glioblastoma (GBM).It is currently considered that an effective T cell immune strategy should improve antigen presentation and recognition and block T cell exhaustion. The main function of γ-interferon-inducible lysosomal thiol reductase (IFI30) is to promote antigen processing and presentation and enhance the anti-tumor effect of cytotoxic lymphocyte (CTL). However, the exact function of IFI30 in GBM development and progression is not yet known. Methods We used multiple public databases to explore the DNA methylation, mRNA transcription and protein expression of IFI30 in GBM, and tried to use the DNA methylation detection data of three cases of GBM to verify the above results. Subsequently, we analyzed the relationship between IFI30, WHO grade and GBM subtype, and studied the diagnostic and prognostic value of IFI30. Further, we combined with public databases to analyze the relationship between IFI30 and immune cell infiltration and immune checkpoints. Finally, we made functional predictions for IFI30 in GBM. Results In GBM, the mRNA transcription level and protein expression level of IFI30 were significantly higher than those in normal tissues. Although the methylation level of IFI30 promoter was decreased, it was significantly increased at local sites. We confirmed the above conclusion after analyzing the DNA methylation detection data of 3 cases of GBM, and found that cg26152923, cg07533630, and cg01485548 were the key prognostic loci after cross-validation. Subsequently, we found that IFI30 was strongly associated with higher WHO grade, MES subtype, and recurrence status of gliomas. At the same time, IFI30 also showed good diagnostic value (AUC = 0.987) and prognostic value. Further, we also found that IFI30 is positively correlated with CD8+ T cells, Treg and other immune cells, and also positively correlated with PD-1, CTLA-4 and other immune checkpoints. Finally, we found that IFI30 may function through Treg development, PPAR signaling pathway, Toll-like receptor signaling pathway and other mechanisms. Conclusions IFI30 could be an ideal diagnostic and prognostic biomarker and therapeutic target for GBM.