Grade II/III Glioma Microenvironment Mining and Its Prognostic Merit

Abstract

The tumor microenvironment greatly influences tumor formation, invasion, and progression. The ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues) algorithm quantifies stromal and immune components in a tumor, reflecting the tumor microenvironment. This study aimed to explore key prognostic genes in a grade II/III glioma microenvironment. We obtained stromal/immune scores for the Cancer Genome Atlas (TCGA) grade II/III glioma cohort from the online ESTIMATE portal. The associations of stromal/immune scores with clinicopathologic characteristics and overall survival of patients with grade II/III glioma were assessed by the Mann-Whitney U test and the Kaplan-Meier method, respectively. Functional enrichment analysis and protein-protein interaction network assessments were employed to analyze differentially expressed genes (DEGs). The top 7 genes with 5 or more edges in the protein-protein interaction network were selected. For validation, CGGA grade II/III glioma data were analyzed. The results showed that elevated stromal/immune/ESTIMATE score was significantly associated with poor survival of patients with TCGA grade II/III glioma. Functional enrichment analysis showed that DEGs were associated with immune cell regulation, extracellular matrix, cytokine activation, and receptor binding. The selected DEGs (interleukin-10, beta-2 microglobulin, C-C motif chemokine ligand 5, cluster of differentiation 74, human leukocyte antigen-DRA, lymphocyte cytosolic protein 2, and myxovirus resistance protein 1) showed prognostic values in patients with grade II/III glioma of the TCGA and CGGA database. Stromal/immune/ESTIMATE scores have prognostic values in patients with grade II/III glioma. The selected DEGs, including interleukin-10, beta-2 microglobulin, C-C motif chemokine ligand 5, cluster of differentiation 74, human leukocyte antigen-DRA, lymphocyte cytosolic protein 2, and myxovirus resistance protein 1, associated with tumor immunity and microenvironment, have prognostic values in grade II/III glioma. Further investigation of these genes could provide novel insights into the tumor microenvironment of glioma.