Prognostic Value and Immune Infiltration of Novel Biomarkers in Glioma: Evidence From a Comprehensive Analysis of Tumor Microenvironment

Abstract BackgroundIn the glioma microenvironment, infiltrating immune cells has been shown to possess beneficial effects for tumor progression. Immune cells and stromal cells dominate the tumor microenvironment in glioma. The complex interplay between the tumor progression with immune cells or stromal cells was still unknown. MethodsIn this study, we used Estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) calculations to calculate the proportion of tumour-infiltrating immune cells (TIC) and the number of immune and stromal components in glioma cases from the cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. Differentially expressed genes (DEG) were analyzed by COX regression analysis and protein-protein interaction (PPI) network construction. Then, JAK3, IL2RB and CD3E were identified as predictors by the intersection analysis of univariate COX and PPI, and further analysis showed that the expression of them were positively correlated with survival and clinicopathological characteristics of glioma patients. Finally, the Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) deconvolution algorithm was applied to quantify the fraction and infiltration of 22 types of immune cells in glioma. ResultsOur results showed that ESTIMATEScores Were Correlated with the Survival of glioma Patients, DEGs Shared by ImmuneScore and StromalScore were predominantly presented as the enrichment of immune-related genes gene set enrichment analysis (GSEA). The intersection analysis of PPI network and univariate COX regression enabled us to identify three genes (JAK3, IL2RB and CD3E) that had never been reported before, whose expression was correlated with clinical characteristics such as survival and WHO grading of these patients. CITICSORT analysis of TIC ratio showed that B cell memory and CD8 + T cells were positively correlated with JAK3, IL2RB and CD3E expression, suggesting that these genes may be responsible for maintaining the immunodominant state of TME. CIBERSORT analysis for the proportion of TICs revealed that the levels of JAK3, IL2RB and CD3E affected the immune activity of TME.ConclusionOur results confirmed that the JAK3, IL2RB and CD3E can be used as diagnostic and prognostic biomarkers for glioma and may be used as therapeutic targets in the future.