Clinicopathological and prognostic value of NADPH oxidase 2 (NOX2) in primary osteosarcoma.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor, particularly among children and adolescents, and the prognosis of osteosarcoma patients remains poor. The NADPH oxidase 2 (NOX2) has been found over-expressed in several human cancers, and closely associated with poor prognosis. Meanwhile the role of NOX2 in osteosarcoma patients has not been reported. This study aimed to investigate the clinicopathological and prognostic significance of NOX2 in osteosarcoma patients. METHODS: Immunohistochemistry (IHC), western blot (WB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of NOX2 in 55 primary osteosarcoma specimens and in 20 non-neoplastic bone tissue specimens. The correlations between NOX2 expression and clinicopathological parameters were analysed by using the χ2 test or Fisher's exact test. Disease free survival and overall survival of osteosarcoma patients were assessed by using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: NOX2 was over-expressed significantly in osteosarcoma compared with that in non-neoplastic bone tissue, and correlated with progression free survival (P < 0.001) and overall survival (P < 0.001). The over-expression of NOX2 was associated with tumor size (P < 0.001), tumor location (P < 0.001). The Cox analysed shown that the over-expression of NOX2 was predicted to be worse PFS (hazard ratio (HR) = 4.10, P = 0.004) and OS (hazard ratio (HR) = 3.50, P = 0.010) time in osteosarcoma patients. CONCLUSIONS: The results of our study suggest that the over-expression of NOX2 is related to adverse clinical outcome, and can be viewed as an independent prognostic marker in osteosarcoma. Further research is required to verify the predictive value of NOX2 in osteosarcoma patients.

Clinicopathological and prognostic values of ErbB receptor family amplification in primary osteosarcoma.

Osteosarcoma is a malignant bone tumor with extremely high invasion, metastasis and mortality. The prognosis of patients with osteosarcoma remains poor. The ErbB receptor family was found to be overexpressed in human cancers and associated with poor prognosis. However, the role of ErbB receptor family in osteosarcoma has not been fully understood. The present study aimed to investigate the clinicopathological and prognostic significances of ErbB receptors in primary osteosarcoma. Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to detect the protein and gene expression of ErbB receptors in 60 primary osteosarcoma specimens and 30 non-neoplastic bone tissues. WB and RT-qPCR analyses showed that the protein and mRNA expression levels of EGFR, ErbB3 and ErbB4 in osteosarcoma specimens were significantly higher than those in non-neoplastic bone tissues. Seventeen (28.33%), 15 (25.00%) and 15 (25.00%) osteosarcoma specimens presented with amplification of EGFR, ErbB3 and ErbB4 gene, respectively, which were significantly higher compared with non-neoplastic bone tissues. The amplification of ErbB3 and ErbB4 in osteosarcoma was associated with advanced surgical stage. The amplification of EGFR, ErbB3, ErbB4 and the co-amplification of EGFR-ErbB3, EGFR-ErbB4, ErbB3-ErbB4 was linked with poor response to chemotherapy and distant metastasis. The amplification of EGFR, ErbB3 and ErbB4, as well as their co-amplification demonstrated independent prognostic values for reduced survival time of osteosarcoma patients and may serve as potential therapeutic targets for osteosarcoma patients in the future.