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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: BMPR2; HIF1-α; immunochemistry; osteosarcoma; survival.

1

The representative immunohistochemical images of bone morphogenetic protein receptor 2 (BMPR2) and hypoxia-inducible factor 1-α (HIF1-α) expression in osteosarcoma tissues. (A) BMPR2-positive; (B) BMPR2-negative; (C) HIF1-α-positive; (D) HIF1-α-negative (100×). The images below show the magnification of each zone (400×).

2

Kaplan-Meier curves showing the impact of bone morphogenetic protein receptor 2 (BMPR2) and hypoxia-inducible factor 1-α (HIF1-α) expression on overall survival (OS) for 103 osteosarcoma patients. (A) BMPR2 (P=0.001); (B) HIF1-α (P<0.001); (C) combined BMPR2 and HIF1-α (P<0.001). +, positive; –, negative.