骨肉瘤血行转移与CXCR4、VEGF相关性研究

Correlation between CXCR4,VEGF and the blood metastasis of osteosarcoma

背景与目的:细胞趋化因子CXCL12及其受体CXCR4在肿瘤转移中起重要作用,在某些肿瘤中,血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)可调节CXCR4的表达以此调节肿瘤侵袭力。本研究在于探讨趋化因子受体CXCR4和VEGF在骨肉瘤组织中的表达及其与血行转移的相关性。方法:应用组织芯片技术检测56例骨肉瘤组织中CXCR4和VEGF表达,分析CXCR4与VEGF之间的相关性及两者与碱性磷酸酶(ALP)、分期等临床特征的相关性,并随访其术后2年内远处血行转移的情况。结果:56例骨肉瘤组织中CXCR4与VEGF表达相关(r=5.678,P=0.02)。单因素分析显示年龄、性别、ALP水平升高与CXCR4、VEGF表达无关,而临床分期与CXCR4、VEGF的表达相关(P=0.026)。56例随访2年内发生远处转移31例,且CXCR4、VEGF表达均与远处转移相关(P值分别为0.018、0.022)。结论:VEGF是骨肉瘤血管生成过程中最重要的正向调节因子,并可能通过调节CXCR4的表达,促进肿瘤细胞向特异性靶器官迁移;CXCR4和VEGF表达可作为骨肉瘤预测血行转移的指标。

Background and purpose： The chemokine, CXCL12 and its receptor, CXCR4, have recently been shown to play an important role in the metastasis of several kinds of carcinoma, It also has been demonstrated that VEGF regulates both the expression of CXCR4 and invasiveness in cancer cell. Our aim was to study the expression of CXCR4, VEGF in osteosarcoma and the correlation between these two factors and distant metastasis. Methods： The immunohistochemical staining SP method was used to detect the expression of CXCR4 and VEGF in 56 cases of osteosarcoma. We analyzed the correlation between the expression of CXCR4 and VEGF, and the correlation between the expression of CXCR4, VEGF and clinical stage, the level of ALP. The patients were followed up for 2 years. Results： There was significant correlation between the expression of CXCR4 and VEGF in 56 cases（r=5.678, P=0.02）. Univariate analysis showed a significant correlation between the expression of CXCR4, VEGF and clinical tumor stage（P=0.026）, and no correlation between the expression of these two factors and age, sex and serum ALP level. 31 cases had metastasis in two years in a total of 56 follow-up cases, and the expression of CXCR4 and VEGF was associate with metastasis（P=0.018 and P=0.022, respectively）. Conclusion： VEGF can upregulate tumor angiogenesis and promote tumor metastasis to specific organ by increasing expression of CXCR4.The increasing expression of CXCR4 and VEGF is useful to predict metastasis and prognosis of osteosarcoma.