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Open Access Highly Accessed Research

Upregulation of SOX9 in osteosarcoma and its association with tumor progression and patients’ prognosis

Haibo Zhu1, Jie Tang1, Mingjie Tang2 and Haikang Cai1*

Author Affiliations

1 Orthopaedics Department, Xuhui central hospital, No. 966, Middle Huaihai Road, Shanghai 200031, China

2 Orthopaedics Department, Shanghai Sixth people's hospital, Shanghai Jiaotong University, Shanghai 200233, China

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Diagnostic Pathology 2013, 8:183  doi:10.1186/1746-1596-8-183

Published: 4 November 2013

Abstract

Objective

SOX9 plays an important role in bone formation and tumorigenesis. However, its involvement in osteosarcoma is still unclear. The aim of this study was to investigate the expression pattern and the clinical significance of SOX9 in human osteosarcoma.

Methods

SOX9 mRNA and protein expression levels were detected by RT-PCR and Western blot assays, respectively, using 30 pairs of osteosarcoma and noncancerous bone tissues. Then, immunohistochemistry was performed to analyze the association of SOX9 expression in 166 osteosarcoma tissues with clinicopathological factors or survival of patients.

Results

SOX9 expression at mRNA and protein levels were both significantly higher in osteosarcoma tissues than those in corresponding noncancerous bone tissues (both P < 0.001). Immunohistochemical staining indicated that SOX9 localized to the nucleus and high SOX9 expression was observed in 120 of 166 (72.3%) osteosarcoma specimens. In addition, high SOX9 expression was more frequently occurred in osteosarcoma tissues with advanced clinical stage (P = 0.02), positive distant metastasis (P = 0.008) and poor response to chemotherapy (P = 0.02). Osteosarcoma patients with high SOX9 expression had shorter overall survival and disease-free survival (both P < 0.001). Furthermore, the multivariate analysis confirmed that upregulation of SOX9 was an independent and significant prognostic factor to predict poor overall survival and disease-free survival (both P = 0.006).

Conclusions

Our data show for the first time that SOX9 is upregulated in aggressive osteosarcoma tissues indicating that SOX9 may participate in the osteosarcoma progression. More importantly, SOX9 status is a useful prognostic factor for predicting the prognosis of osteosarcoma, suggesting that SOX9 may contribute to the optimization of clinical treatments for osteosarcoma patients.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1318085636110837 webcite.

Keywords:
Osteosarcoma; SOX9; Prognosis; Overall survival; Disease-free survival