Identification of MAP3K15 as a Potential Prognostic Biomarker and Correlation with Immune Infiltrates in Osteosarcoma

Abstract Background: Osteosarcoma (OS) is a type of primary malignant tumor, and increasing amounts of evidence show the clinical benefits of immunotherapy in treating OS. However, the lack of comprehensive studies on the complex OS immune microenvironment hinders the application of immunotherapy. Thus, we aimed to systematically study the immune characteristics of OS and identify novel biomarkers for OS treatment.Methods: We systematically studied the immune score and proportion of infiltrating immune cells in OS in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases using the ESTIMATE and CIBERSORT algorithms. Differential expression and functional analyses were used to identify dysregulated genes and explore their functions. Survival and Cox regression analyses were applied to establish an immune-related prognostic signature. The expression of MAP3K15 was performed by qPCR assay and immunohistochemistry. We divided 48 patients into high expression and low expression groups according to MAP3K15 expression.Results: A total of 103 differentially expressed immune genes (DEIGs) were found in the TARGET-OS and GSE39058 databases, and these DEIGs were mainly enriched in leukocyte proliferation, leukocyte differentiation, osteoclast differentiation, natural killer (NK) cell-mediated cytotoxicity and the adaptive immune system. A predictive signature was constructed based on the survival analysis, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.65. Moreover, we found that mitogen-activated protein kinase kinase kinase 15 (MAP3K15) can predict the prognosis of patients with OS and is closely related to CD4 T cells, M0 macrophages, and M1 macrophages. We found that patients with high MAP3K15 expression had a significantly poorer prognosis Conclusions: Our study found that MAP3K15, whose expression level is closely related to immune activity in tumors, was a critical immune-related biomarker and may provide a basis for OS immunotherapy. Clinical Trial RegistrationNot applicable.