• Jiawei Chen, Chongxian Hou, Peng Wang, Yong Yang, and Dong Zhou.
• Department of Neurosurgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Shantou University Medical College, Shantou, Guangdong, China.
• World Neurosurg. 2019 Dec 1; 132: e76-e88.

ObjectiveThe 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.MethodsWe 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.ResultsThe 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.ConclusionsStromal/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.Copyright © 2019 Elsevier Inc. All rights reserved.

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