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Ann Med.2025 Dec 01;57(1):2593209.doi:10.1080/07853890.2025.2593209
Abstract
BACKGROUND: Gliomas are aggressive central nervous system tumors with limited understanding of their molecular drivers. Identifying novel prognostic and therapeutic biomarkers remains crucial.
METHODS: Using TCGA, GTEx, GEO, and CGGA datasets, we performed differential expression, Cox regression, and LASSO analyses to identify prognostic genes. IFI44, one of eight significant candidates, was analyzed for its association with survival, clinical features (IDH mutation, 1p/19q codeletion) and tumor immune microenvironment. Functional assays were conducted to evaluate its effects on glioma cell proliferation, migration, and invasion.
RESULTS: Transcriptomic analysis of 1,142 normal and 398 glioma samples identified 61 consistently dysregulated genes, predominantly enriched in immune-related rather than classical oncogenic pathways. In CGGA cohorts, eight progression-associated genes were identified, six associated with poor prognosis. IFI44 expression correlated with higher grade, older age, IDH wild type, and 1p/19q non-codeletion. High IFI44 tumors were enriched for NF1 mutations, while low IFI44 tumors carried IDH1, NOTCH1, and CIC mutations. Mechanistically, IFI44-high gliomas exhibited immune-suppressive pathway enrichment, increased checkpoint expression (PD-1/PD-L1, CTLA4, LAG3), and macrophage infiltration. Protein interaction analysis linked IFI44 to cytokine signaling and T-cell regulation. In U87 and U251 cells, IFI44 overexpression promoted proliferation, migration, and invasion, whereas knockdown suppressed these phenotypes.
CONCLUSIONS: IFI44 may drive glioma progression through dual mechanisms of immune microenvironment remodeling and promotion of tumor cell aggressiveness, supporting its potential as a prognostic biomarker and therapeutic target. Although preliminary knockdown and overexpression assays were performed, the underlying mechanisms of IFI44-mediated immune regulation and tumor progression require further investigation.
