Prognostic role of the recepteur d'origine nantais (RON) expression in primary high-grade osteosarcoma

Abstract

Background: Osteosarcoma is a common primary malignant bone tumor susceptible to distant metastasis. The clinical outcome for patients remains poor due to the resistance to chemotherapy and lacking effective therapeutic targets. Recepteur d'origine nantais (RON), a transmembrane protein of the c-MET proto-oncogene family, has been reported to contribute to the malignant progression and bone metastasis in several tumors. The present study aimed to explore the prognostic significance of RON in primary high-grade osteosarcoma.

Methods: Immunohistochemistry (IHC) and western blotting (WB) were used to investigate the protein expression of RON in 80 surgically resected specimens (50 high-grade osteosarcoma specimens and 30 non-neoplastic bone tissues) and 6 cell lines. The χ² test or independent-sample Student's t-test was used to assess the significance of RON difference between osteosarcoma and non-neoplastic bone tissues. The χ² test and Fisher's exact test were used to analyze the association of RON with the clinicopathological features of osteosarcoma patients. Kaplan-Meier method and Cox proportional hazards model were used to assess the significance of RON for the survival of osteosarcoma patients.

Results: The results of IHC and WB observed significant overexpression of RON in osteosarcoma specimens (P < 0.001) and osteosarcoma cell lines. Moreover, immunohistochemical high expression of RON was associated with a poor response to chemotherapy (P = 0.032) as well as worse progression-free (P = 0.003) and overall (P < 0.001) survival of osteosarcoma patients. Multivariate analysis revealed that high expression of RON was independently associated with reduced progression-free (P = 0.027, HR = 2.31) and overall survival (P = 0.004, HR = 5.06) time of osteosarcoma patients.

Conclusions: The present study demonstrated that high expression of RON held independent value for unfavorable survival in primary high-grade osteosarcoma. Its potential role as a therapeutic target for osteosarcoma treatment deserves further research.