The Value of Immune-Related Genes Signature in Osteosarcoma Based on Weighted Gene Co-expression Network Analysis

Abstract

Background. Osteosarcoma (OS) is a serious malignant tumor that is more common in adolescents or children under 20 years of age. This study is aimed at obtaining immune-related genes (IRGs) associated with the progression and prognosis of OS. Method. Expression profiling data and clinical data for OS were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. ESTIMATE calculates immune scores and stromal scores of samples and performs the prognostic analysis. Weighted gene coexpression network analysis (WGCNA) was used to find modules correlated with immune and stromal scores. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were used to explore IRGs associated with OS prognosis and construct and validate a hazard score model. Finally, we verified the expression and function of EVI2B in OS. Results. WGCNA selected twenty-eight IRGs, 10 of which were associated with OS prognosis, and LASSO further obtained three key prognostic genes. A prognostic model of EVI2B was constructed, and according to the risk score model, patients in the high-risk group had a worse prognosis than those in the low-risk group, and the prognosis was statistically significant in the high- and low-risk groups. Receiver operating characteristic (ROC) curves were used to assess the prognostic model’s accuracy and externally validate the independent GSE21257 cohort. The results of immunohistochemical staining and qPCR showed that EVI2B was a tumor suppressor gene. The differential genes in the high- and low-risk groups were analyzed by enrichment analysis of GO and KEGG, indicating that the EVI2B model is associated with immune response. Conclusion. In this study, IRG EVI2B is closely related to OS’s prognosis and can be used as a potential biomarker for prognosis and treatment of OS.