Abstract
ObjectiveSOX9 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.MethodsSOX9 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.ResultsSOX9 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).ConclusionsOur 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 slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1318085636110837.
Highlights
Osteosarcoma, a kind of highly aggressive neoplasm arising from long bones, is the most common primary malignancy in children and adolescents [1]
Upregulation of SOX9 at mRNA and protein levels in human osteosarcoma tissues As shown in Figure 1A, the expression levels of SOX9 mRNA were found to be distinctly increased in osteosarcoma tissues compared to noncancerous bone tissues
The statistic analysis showed that the relative level of SOX9 mRNA expression in osteosarcoma tissues was significantly higher than that in corresponding noncancerous bone tissues
Summary
Osteosarcoma, a kind of highly aggressive neoplasm arising from long bones, is the most common primary malignancy in children and adolescents [1]. It is a relative uncommon cancer with an estimated worldwide incidence of 2 ~ 3 cases per million persons per year, osteosarcoma rates for patients with osteosarcoma are around 50-60% [4]. In order to give effective treatment to each patient, accumulating studies have tried to predict the clinical course of osteosarcoma patients by assessing the response to chemotherapy histologically or by determining clinical stage. We further revealed the clinical significance of the aberrant expression of SOX9 in this disease
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