EVI2B Is a Prognostic Biomarker and Is Correlated with Monocyte and Macrophage Infiltration in Osteosarcoma Based on an Integrative Analysis

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor. However, treatment strategies have not changed over the past 30 years. The relationship between OS and the immune microenvironment may provide a basis for the establishment of novel therapeutic targets. In this study, a large-scale gene expression dataset (GSE42352) was used to identify key genes in OS. A Target-OS dataset from the Cancer Genome Atlas was used as a validation set. Ecotropic viral integration site 2B (EVI2B) was significantly upregulated in OS tumor samples. Differentially expressed genes (DEGs) were identified between samples with high and low EVI2B expression in both the test and validation cohorts. The top three functions of DEGs determined by a gene set enrichment analysis (GSEA) were chemokine signaling, cytokine–cytokine receptor interaction, and Human T-cell leukemia virus 1 infection. A prognostic prediction model including EVI2B, DOCK2, and CD33 was constructed by a Cox regression analysis. This model indicated that EVI2B is an independent protective prognostic marker in OS. An analysis of immune infiltration further showed that high EVI2B expression levels were correlated with high levels of macrophage infiltration. Protein expression data derived from the Human Protein Atlas suggested EVI2B to be highly expressed in monocytes. Finally, we validated the elevated expression of EVI2B in OS cell lines and OS tissue samples; these results were consistent with those of the analyses of the GSE42352 and Target-OS datasets. Our integrative bioinformatics analysis and experimental results provide clear evidence for the prognostic value of EVI2B in OS and its close relationship with monocyte and macrophage infiltration.

Keywords

• osteosarcoma
• EVI2B
• macrophage infiltration
• gene set enrichment analysis
• prognostic model