Slit分泌蛋白家族2/Slit分泌蛋白家族特异性受体1在骨髓增生异常综合征中的表达及意义

Expression and clinical significance of Slit2/Robo1 in myelodysplastic syndrome

目的探讨Slit分泌蛋白家族2/Slit分泌蛋白家族特异性受体1(Slit2/Robo1)在骨髓增生异常综合征(MDS)中的表达及临床意义。方法以2017年8月至2019年6月就诊于徐州医科大学附属医院的51例初诊MDS病人为研究对象,采用Ficoll密度梯度离心法分离51例MDS病人治疗前后骨髓单个核细胞,并通过实时定量PCR检测细胞中Slit2/Robo1mRNA的表达水平,采用蛋白质印迹法(Westernblotting)测定其蛋白表达。将Slit2/Robo1mRNA表达水平与临床参数进行相关性分析。以对照组Slit2、Robo1 mRNA表达水平为基线,分别将Slit2、Robo1 mRNA的表达量分为高表达组和低表达组,Kaplan-Meier法绘制生存曲线,并分析Slit2/Robo1 mRNA基因表达水平与MDS预后关系。结果初治组Robo1表达量明显高于正常对照组[(2.595±0.395)比(1.422±0.485)],而Slit2表达量明显低于正常对照组[(2.453±0.185)比(2.729±0.136)](P<0.05);中高危病人治疗后,有效组Robo1表达量降低,无效组升高,Slit2表达量则相反,有效组较前升高,无效组较前降低(P<0.05)。相关性分析结果显示,Robo1 mRNA表达水平与IPSS-R分组、骨髓原始细胞数、年龄均呈正相关(r=0.36,r=0.41,r=0.36),Slit2 mRNA表达水平与IPSS-R分组、骨髓原始细胞数、年龄均呈负相关(r=−0.83,r=−0.78,r=−0.53)。生存分析显示Robo1 mRNA相对表达水平与病人的总生存期(OS)及无进展生存期(PFS)呈负相关,而Slit2mRNA水平与病人的总生存期(OS)及无进展生存期(PFS)呈正相关(P<0.05)。结论Slit2/Robo1在MDS病人骨髓单个核细胞中表达,其在MDS的发生、发展及预后中起重要作用。

Objective To investigate the expression and clinical significance of Slit2/Robo1 in myelodysplastic syndrome(MDS).Methods Fifty-one newly diagnosed MDS patients who were treated in the Affilliated Hospital of Xuzhou Medical University from August 2017 to June 2019 were selected as the research objects.Ficoll density gradient centrifugation method was used to isolate the bone marrow mononuclear cells from 51 patients with myelodysplastic syndrome before and after treatment.The expression level of Slit2/Robo1 mRNA in the cells was detected by real-time quantitative PCR,and the protein expression was measured by Western blot.And the correlation between the expression level of Slit2/Robo1 mRNA and clinical parameters was analyzed.Based on the expression levels of Slit2 and Robo1 mRNA in the control group,the expressions of Slit2 and Robo1 mRNA were divided into high expression group and low expression group,respectively.The survival curve was drawn by Kaplan-Meier method,and the relationship between the gene expression levels of Slit2/Robo1mRNA and the prognosis of MDS was analyzed.Results The expression of Robo1 in the initial treatment group was significantly higher than that in the normal control group[(2.595±0.395)vs.(1.422±0.485)],while the expression of Slit2 in the middle and high risk group was significantly lower than that in the normal control group[(2.453±0.185)vs.(2.729±0.136)](P<0.05).After treatment,the expression of Robo1 in the effective group decreased,while that in the ineffective group increased,on the contrary,the expression of Slit2 in the effective group increased and decreased in the ineffective group(P<0.05).The results of correlation analy⁃sis showed that Robo1 mRNA expression level was positively correlated with IPSS-R grouping,bone marrow primordial cell number and age(r=0.36,r=0.41,r=0.36),while Slit2 mRNA expression level was negatively correlated with IPSS-R grouping,bone marrow primordial cell number and age(r=−0.83,r=−0.78,r=−0.53).Survival analysis showed that the relative expression level of Robo1 mRNA was negatively correlated with overall survival(OS)and progression-free survival(PFS),while Slit2 mRNA level was positively correlated with overall survival(OS)and progression-free survival(PFS).Conclusion Slit2/Robo1 is expressed in bone marrow mononuclear cells of patients with MDS,and may play an important role in the occurrence,development and prognosis of MDS.