急性髓细胞白血病患者外周血单核细胞IL-9、STAT3和miR-21的表达及意义

Expressions and clinical significance of IL-9,STAT3,and miR21 in the peripheral blood mononuclear cells of patients with acute myeloid leukemia

目的探讨急性髓细胞白血病(Aml)患者外周血单核细胞(PBMCs)中白介素-9(IL-9)、信号转导与转录活化因子3(STAT3)和miR-21的表达及临床意义。方法选取2011年2月至2014年6月住院治疗的120例Aml患者为研究对象(Aml组),以同时期的健康体检者100例为对照组,采用RT-PCR检测所有受试者PBMCs中IL-9、STAT3和miR-21mRNA的表达水平,Western blot法检测IL-9和磷酸化STAT3(pSTAT3)蛋白表达,Spearman分析IL-9、STAT3和miR-21表达之间相关性,ROC曲线分析IL-9、STAT3、miR-21及三者联合检测对Aml的诊断价值,Kaplan-Meier法分析IL-9、STAT3和miR-21表达对Aml患者生存期影响。结果与对照组相比,Aml组患者PBMCs中IL-9、STAT3和miR-21mRNA表达水平均上调(P<0.05),IL-9和pSTAT3蛋白表达显著增加(P<0.05)。IL-9、STAT3和miR-21mRNA水平与患者年龄、性别、血红蛋白均不相关(P>0.05),与FBA分型、白细胞计数和骨髓原始细胞相关(P<0.05),IL-9与血小板计数相关(P<0.05)。Spearman相关性分析结果显示,IL-9与miR-21、IL-9与STAT3以及miR-21与STAT3表达均呈正相关(r=0.467,P<0.05;r=0.527,P<0.05;r=0.483,P<0.05)。IL-9、STAT3和miR-21三者联合诊断ALM的灵敏度、特异度以及ROC曲线下面积均较单独诊断时显著提高(P<0.05)。IL-9、STAT3和miR-21高表达患者生存期均较低表达患者显著降低(P<0.05)。结论Aml患者PBMCs中IL-9、STAT3和miR-21均表达升高,IL-9可能通过STAT3信号通路诱导miR-21表达上调参与Aml疾病的发生发展过程。

Objective To investigate the expressions and clinical significance of interleukin-9(IL-9),signal transduction and transcription activator 3(STAT3),and miR21 in peripheral blood mononuclear cells(PBMCs)of patients with acute myeloid leukemia(Aml).Methods A total of 120 patients with Aml who were admitted and treated in our hospital from February 2011 to June 2014 were enrolled as Aml group,at the same time,the other 100 healthy subjects who underwent physical examination were enrolled as control group.The expression levels of IL-9,STAT3,and miR21 in PBMCs of all subjects were detected by RT-PCR,and the protein expressions of IL-9 and phosphorylated STAT3(pSTAT3)were detected by Western Blot.The correlation among the expressions of IL-9,STAT3 and miR21 was analyzed by means of Spearman analysis.The diagnostic value of IL-9,STAT3,miR21,and the combination detection of the three factors for Aml was analyzed by means of ROC curve.Moreover the effects of IL-9,STAT3,and miR21 expressions on the survival duration of patients with Aml were analyzed by Kaplan Meier method.Results The mRNA expressions of IL-9,STAT3 and miR21 of PBMCs in Aml group were significantly upregulated,as compared with those in control group(P<0.05),moreover the protein expressions of IL-9 and pSTAT3 of PBMCs in Aml group were significantly increased,as compared with those in control group(P<0.05).The mRNA levels of IL-9,STAT3 and miR21 were not correlated with patient’s age,sex,and hemoglobin levels(P>0.05),however,which were positively correlated FBA typing,white blood cell count,and bone marrow primordial cells(P<0.05).Moreover the expression of IL-9 was correlated with platelet count(P<0.05).Spearman correlation analysis showed that there were a positive correlation between the expression levels of IL-9 and miR21,TAT3,miR21 and those of STAT3(P<0.05).In addition the sensitivity,specificity,and area under ROC curve of combined diagnosis of IL-9,STAT3 and miR21 for ALM were significantly higher than those by single index diagnosis(P<0.05).The survival time of patients with high expressions of IL-9,STAT3 and miR21 were significantly lower than those of patients with low expressions of IL-9,STAT3 and miR21(P<0.05).Conclusion The expressions of IL-9,STAT3 and miR21 of PBMCs in patients with Aml are increased.IL-9 may be involved in the pathogenesis and development of Aml by upregulating the expression of miR21 through STAT3 signaling pathway.