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Highlights • The SOX9 expression increased in tumor tissues and peripheral blood of malignant and benign bone tumors. • The protein level of SOX9 is enhanced in malignant bone tumor tissues. • SOX9 over-expression correlated with tumor severity, grade, invasion feature, poor response to therapy, and recurrence. Purpose The status of the local and circulating SOX9, a master regulator of the tumor fate, and its relevance to tumor types, severity, invasion feature, response to therapy, and chemotherapy treatment were surveyed in bone cancer in the current study. Methods The SOX9 expression level was evaluated in tissue and peripheral blood mononuclear cells from patients with different types of malignant and benign bone tumors also tumor margin tissues using Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry and western blot analysis. Also, the correlations of the SOX9 expression level with the patient’s clinical and pathological features were considered. Results The remarkable overexpression of SOX9 was detected in bone tumors compared to tumor margin tissues (P |