BMPR2 and HIF1-α overexpression in resected osteosarcoma correlates with distant metastasis and patient survival.

Abstract

Bone morphogenetic protein receptor 2 (BMPR2) and hypoxia-inducible factor 1-α (HIF1-α) existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown. To investigate the clinical significance of BMPR2 and HIF1-α in osteosarcoma, we analyzed their expression levels in 103 osteosarcoma specimens by immunochemistry. Meanwhile, we conducted a follow-up to examine the metastatic behavior and overall survival (OS) of osteosarcoma patients. Among 103 tissues, 61 cases had BMPR2-positive expression and 57 cases had HIF1-α positive expression. A significant correlation was noticed between BMPR2 and HIF1-α expression in osteosarcoma specimens (P=0.035). Receiver-operating characteristic (ROC) curves were calculated to investigate the predictive value of the two markers in tumor metastasis. By means of univariate and multivariate analysis, BMPR2 and HIF1-α expression, as well as higher tumor grade, were identified as significant risk factors for OS in patients with osteosarcoma. Kaplan-Meier survival analysis revealed that the patients with BMPR2 and HIF1-α positive expression had worse OS compared with patients with BMPR2-negative or HIF1-α-negative staining. It can be concluded that BMPR2 and HIF1-α expression is highly correlated with metastatic behavior in patients with osteosarcoma and can serve as predictive markers for metastasis and OS of these patients.