骨肉瘤顺铂化疗耐药与FoxM1、Rad50的关系及临床意义

Clinical relation of FoxM1 and Rad50 expression with cisplatin chemotherapy resistance in osteosarcoma

目的探讨FoxM1和DNA修复基因Rad50在骨肉瘤细胞、临床组织样本中的表达及与临床病理特征的关系。方法收集84例骨肉瘤均有完整的临床、影像和随访资料;采用qRT-PCR、Western blot法检测2株亲本骨肉瘤细胞与顺铂耐药细胞中FoxM1和Rad50 mRNA及蛋白水平的表达;应用免疫组化法检测84例临床骨肉瘤组织中FoxM1和Rad50蛋白表达,并分析其表达与临床病理特征及预后的关系。结果 qRT-PCR和Western blot结果显示:FoxM1和Rad50 mRNA及蛋白水平在耐药细胞中表达较亲本细胞明显增高;免疫组化结果显示:FoxM1及Rad50在骨肉瘤组织中的高阳性率分别为33.33%和38.10%,与低表达患者相比,高表达患者总生存率较低、Enneking分期较高,差异有统计学意义(P<0.05);与患者年龄、性别、部位、组织学类型等其它临床病理因素差异均无显著性(P>0.05);相关性分析显示FoxM1和Rad50表达呈正相关(r_s=0.390,P<0.01)。结论 FoxM1和Rad50可作为预测骨肉瘤生物学不良行为的指标,有望成为逆转骨肉瘤化疗耐药的潜在靶点。

Purpose To investigate the expression and clinical relation of FoxM1 and Rad50 expression in osteosarcoma samples and osteosarcoma cell lines. Methods A total of 84 osteosarcoma samples were collected. All cases had complete clinical, imaging and follow-up data. The FoxMl and Rad50 mRNA and protein level of FoxMl and Rad50 were detected by qRT-PCR and Western blot analysis in two cisplatin resistant cells and parental osteosarcoma cells. Immunohistochemical staining of FoxMl and Rad50 was performed in 84 cases of osteosarcoma samples, and the relationship between the expression and clinical pathological factors and prognosis was analyzed. Results Both mRNA and protein level of FoxMl and Rad50 significantly increased in cisplatin resistant cells compared with parental osteosarcoma cells. The high expression rates of FoxM1 and Rad50 in osteosarcoma samples were 33. 33% and 38. 10%, respectively. High expression of FoxMl and Rad50 was found to be significantly associated with poor clinical outcomes in overall survival and high Enneking stage,but not with age, sex, location, histological type and other clinicopathologic factors. Spearman rank sum test showed that there was a positive correlation between FoxMl and Rad50 expression（rs =0. 390, P 0. 01）. Conclusion The results suggest that high expression of FoxM1 and Rad50 is a predictive biomarker for poor outcome. FoxM1 and Rad50 could be used as potential targets to overcome osteosarcoma chemoresistance.