Correlation of AIF-1 Expression with Immune and Clinical Features in 1270 Glioma Samples

AIF-1 gene is surrounded by the genes involved in the inflammatory response and located in the major histocompatibility complex (MHC) class III genomic region. It has been found that microglial cells expressed the AIF-1 gene during all stages of mice brain development. However, the role of AIF-1 remains unclear in glioma. A total of 1270 glioma patients from three independent data sets were enrolled in the study. TIMER platform was used for comprehensive molecular characterization of tumor immune infiltrates. Sangerbox was used to analyze AIF-1 RNA sequencing expression data of tumors and normal samples, and to evaluate the association between AIF-1 expression and 29 sub-populations of immune cells. The R language 3.63 was used to identify differentially expressed genes for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Kaplan-Meier survival analysis and univariate/multivariate Cox analysis were used to examine survival distributions. We found that AIF-1 gene was prominently up-regulated, especially in brain glioma including LGG and GBM. A strong correlation was observed between AIF-1 expression and the majority of immune cells, particularly in macrophage, myeloid-derived suppressor cells. Moreover, AIF-1 expression was correlated with immune infiltration level. We found that AIF-1 expression was strongly correlated with the specific immune and prognostic cell markers of monocytes, microglia and macrophages, M1 macrophages, and M2 macrophages after normalization through tumor purity in TCGA-LGG and TCGA-GBM. Higher expression level of AIF-1 was found to be significantly correlated with poor prognosis. GO analysis and KEGG pathways indicated that AIF-1 could affect glioma-related immune activities. Our study suggests that AIF-1 can be treated as a prognostic biomarker for glioma patients. AIF-1 was involved in pro-tumor processes and the regulation of immune status and correlates with poor prognosis.