Hosseini Ameinh, Mirzaei Alireza, Salimi Vahid, Jamshidi Khodamorad, Babaheidarian Pegah, Fallah Soudabeh, Rampisheh Zahra, Khademian Narges, Abdolvahabi Zohreh, Bahrabadi Mehrdad, Ibrahimi Mostafa, Hosami Fatemeh, Tavakoli-Yaraki Masoumeh
Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran.
J Bone Oncol. 2020 May 31;23:100300. doi: 10.1016/j.jbo.2020.100300. eCollection 2020 Aug.
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.
The 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 expression level with the patient's clinical and pathological features were considered.
The remarkable overexpression of was detected in bone tumors compared to tumor margin tissues ( < 0.0001). Malignant bone tumors revealed a higher expression of compared to benign tumors ( < 0.0001) while osteosarcoma tumors showed higher expression levels compared to Ewing sarcoma, and chondrosarcoma. Overexpression of was observed in high grade, metastatic, recurrent tumors also tumors with poor response to therapy. Besides, the patients under the chemotherapy treatment demonstrated higher levels of compared to the rest of malignant tumors ( = 0.02). The simultaneous up-regulation of circulating in the patients with bone cancer was observed compared to healthy individuals ( < 0.0001) accompanying with overexpression of in malignant tumors compared to benign tumors (P < 0.0001). The circulating expression was up-regulated in the patients with malignant bone tumors who receive chemotherapy treatment also patients with high grade, metastatic, recurrent tumors. The protein level of SOX9 was in line with our data on the gene expression.
The simultaneous overexpression of local and circulating SOX9 in bone cancer besides its positive correlation with tumor severity, malignancy, size, and chemotherapy may deserve receiving more attention in bone cancer diagnosis and therapy.
在本研究中，调查了肿瘤命运的主要调节因子——局部和循环中的SOX9的状态，及其与骨癌的肿瘤类型、严重程度、侵袭特征、治疗反应和化疗的相关性。
使用实时聚合酶链反应（Real-Time PCR）评估不同类型恶性和良性骨肿瘤患者的组织及外周血单核细胞以及肿瘤边缘组织中SOX9的表达水平。使用免疫组织化学和蛋白质印迹分析评估SOX9的蛋白水平。此外，还考虑了SOX9表达水平与患者临床和病理特征的相关性。
与肿瘤边缘组织相比，骨肿瘤中检测到SOX9明显过表达（P<0.0001）。恶性骨肿瘤与良性肿瘤相比，SOX9表达更高（P<0.0001），而骨肉瘤肿瘤与尤文肉瘤和软骨肉瘤相比，显示出更高的表达水平。在高级别、转移性、复发性肿瘤以及对治疗反应不佳的肿瘤中观察到SOX9过表达。此外，接受化疗的患者与其他恶性肿瘤患者相比，SOX9水平更高（P=0.02）。与健康个体相比，骨癌患者循环中的SOX9同时上调（P<0.0001），恶性肿瘤中SOX9的过表达高于良性肿瘤（P<0.0001）。接受化疗的恶性骨肿瘤患者以及高级别、转移性、复发性肿瘤患者的循环SOX9表达上调。SOX9的蛋白水平与我们关于SOX9基因表达的数据一致。
骨癌中局部和循环SOX9的同时过表达及其与肿瘤严重程度、恶性程度、大小和化疗的正相关，可能值得在骨癌诊断和治疗中给予更多关注。
