转录因子TWIST2在儿童急性髓系白血病中的表达与预后意义研究

The expression and prognostic significance of transcription factor TWIST2 in pediatric acute myeloid leukemia

目的研究转录因子Twist相关蛋白2基因(Twist related protein2,TWIST2)在急性髓系白血病(acute myeloid leukemia,AML)中的表达及预后意义。方法通过TARGET数据库中AML患者临床资料及RNA表达数据,研究TWIST2在AML患者中的表达及其与患者临床资料的相关性。结果AML患者TWIST2表达水平与FLT3-ITD突变、inv(16)、FAB分型及细胞遗传学分组密切相关(均P<0.05)。受试者操作特征曲线(receiver operating characteristic curve,ROC曲线)示TWIST2表达水平可预测患者长期预后,最佳截点值为0.010,曲线下面积为0.621(P=0.009),敏感性为73.8%,特异性为55.3%。据此,将患者分为高表达组与低表达组。TWIST2高表达组患者无事件生存率(event-free survival,EFS)与总生存(overall survival,OS)率均明显劣于低表达者。单因素分析示FLT3-ITD突变、CEBPA突变、细胞遗传学分组与患者EFS相关;FLT3-ITD突变、细胞遗传学分组、TWIST2表达水平与患者OS相关。多因素分析示FLT3-ITD突变、细胞遗传学分组与患者EFS有关,而FLT3-ITD突变、细胞遗传学分组、TWIST2表达水平与患者OS相关。结论AML患者TWIST2表达水平与患者临床特征有一定相关性,可能为患者独立的不良预后因素之一。

Objective To investigate the expression and prognostic significance of transcription factor Twist related protein2 gene(TWIST2)in patients with acute myeloid leukemia(AML).Method Clinical and RNA expression data of patients with AML were extracted from Therapeutically Applicable Research To Generate Effective Treatments(TARGET)database to study the associations between TWIST2 expression and clinical characteristics of patients with AML.Result The levels of TWIST2 expression were significantly associated with FLT3-ITD mutation,inv(16),FAB classification,and cytogenetic risk groups(all P<0.05).Receiver operating characteristic curve(ROC curve)were used to predict the outcome of patients.The optimal cutoff value was 0.010,with area under curve of 0.621(P=0.009),the sensitivity of 73.8%,and the specificity of 55.3%.Patients with high TWIST2 expression levels showed significantly inferior event-free survival(EFS)and overall survival(OS).Univariate analysis showed that FLT3-ITD mutation,CEBPA mutations,and cytogenetic risk groups were related to EFS,and FLT3-ITD mutation,cytogenetic risk groups,and TWIST2 expression levels were associated with OS.Multivariate analysis demonstrated that FLT3-ITD mutation,cytogenetic risk groups were associated with EFS,while FLT3-ITD mutation,cytogenetic risk groups,and TWIST2 expression levels were related to OS.Conclusion The expression levels of TWIST2 were significantly associated with clinical characteristics of patients with AML,and a high level of TWIST2 expression may be an independent risk factor for patient with AML.