BMPR2 expression level is correlated with low immune infiltration and predicts metastasis and poor survival in osteosarcoma.

Abstract

Osteosarcoma is the most common malignant bone tumor in adolescents and young adults, and identifying biomarkers for prognosis and therapy is necessary. Bone morphogenetic protein receptor 2 (BMPR2) is involved in various cellular functions, including cell adhesion, proliferation and invasion, inflammation, apoptosis and metastatic spread. However, the correlation between BMPR2 expression levels and prognosis and tumor-infiltrating immune cells in osteosarcoma is not well understood. In the present study, the expression level of BMPR2 was investigated using the Oncomine and R2 databases. The association between the expression level of BMPR2 and the clinical prognosis of patients with cancer was analyzed using the R2 database. The relationship between the expression level of BMPR2 and immune cell infiltration in the stroma of osteosarcoma was assessed using the Tumor Immune Estimation Resource (TIMER) and CIBERSORT. The correlations between BMPR2 expression level and infiltrated immune cell gene marker sets in osteosarcoma were validated in the TIMER and R2 databases. Analysis of a cohort of patients with osteosarcoma revealed that BMPR2 expression was significantly higher in osteosarcoma compared with in normal tissue and was correlated with poor prognosis. M0 macrophages, M2 macrophages, resting mast, γ δ T and CD8+ T cells were the top five immune cells with the highest degrees of infiltration in osteosarcoma. In addition, BMPR2 expression level showed a significant negative correlation with the gene markers of CD8+ T cells, monocytes and M2 macrophages. Low levels of infiltrating CD8+ T cells, monocytes or M2 macrophages in osteosarcoma was significantly associated with poor survival. These data suggested that CD8+ T cells, monocytes and M2 macrophages play significant roles in the establishment of the immune microenvironment of osteosarcoma. High BMPR2 expression was associated with poor prognosis and low infiltration of CD8+ T cells, monocytes and M2 macrophages in osteosarcoma. Hence, BMPR2 can be considered a biomarker of the immune infiltration, metastasis and prognosis of osteosarcoma.