IFN-γ Triggered IFITM2 Expression to Induce Malignant Phenotype in Elderly GBM

Abstract

Advanced age is an important risk factor for the worse clinical presentation of gliomas, especially glioblastoma (GBM). The tumor microenvironment (TME) in elderly GBM (eGBM) patients is considerably different from that in young ones, which causes the inferior clinical outcome. Based on the data from the Chinese Glioma Genome Atlas RNA sequence (CGGA RNA-seq), the Cancer Genome Atlas RNA array (TCGA RNA-array), and gene set enrichment (GSE) 16011 array sets, the differential genes and function between eGBM (≥ 60 years old) and young GBM (yGBM, 20–60 years old) groups were explored. Immunohistochemistry (IHC) was utilized to depict the abundance of CD8⁺ cells (the main resource of IFN-γ) and IFITM2 protein expression in GBM samples. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting (WB) were performed to verify the link between IFN-γ and IFITM2. Moreover, the small-interfering RNA (siRNA) of IFITM2 was used to explore the function of IFITM2 in GBM. Characterized by inflammatory TME and higher IFITM2 expression, eGBM harbored a shorter survival time. Chemotaxis and inflammatory cytokine-related genes were enriched in the eGBM group, with more infiltrative CD8⁺ T cells. The IHC of CD8 and IFITM2-staining could demonstrate these results. In addition, the IFN-γ response pathway was activated in eGBM and resulted in a dismal outcome. Next, it was found that IFITM2 triggered by IFN-γ played a key role in IFN-γ-induced malignant phenotype in eGBM.