联合检测E2F3a和CASP8AP2表达水平在儿童急性淋巴细胞白血病预后中的意义

The role of combined analysis of E2F3a and CASP8AP2 expression in prognosis evaluation in pediatric acute lymphoblastic leukemia

目的探讨联合检测E2F3a和CASP8AP2的表达水平在儿童急性淋巴细胞白血病（ALL）预后判断中的意义。方法选取2008年3月至2010年7月首都医科大学附属北京儿童医院血液肿瘤中心收治的初诊ALL患儿141例，其中男97例，女44例；确诊时年龄1.2～15.5岁，中位数5.2岁。采用实时荧光定量PCR（qPCR）方法检测141例ALL患儿的E2F3a和CASP8AP2的基因表达水平。利用受试者工作特征（ROC）曲线确定E2F3a和CASP8AP2表达水平的最佳分界点，将患儿分为高表达组和低表达组，比较其预后差异。Cox回归方法分析E2F3a和CASP8AP2的联合表达水平的预后意义。结果E2F3a和CASP8AP2双低表达组儿童ALL的5年无复发生存（RFS）率、无病生存（EFS）率和总生存（OS）率分别为（58.9±10.0）%、（56.0±9.9）%和（72.0±9.0）%，均明显低于双高表达组[（94.9±2.5）%、（93.7±2.7）%和（96.2±2.2）%]，差异均有统计学意义（均P〈0.05）。E2F3a和CASP8AP2 2个基因均低表达的患儿与其他患儿相比，其预后很差；2个基因均低表达与MLL重排、诱导治疗结束时微小残留病水平是儿童ALL的独立预后因素。结论初诊E2F3a和CASP8AP2低表达的ALL患儿预后差，联合分析E2F3a与CASP8AP2 2个基因的表达水平能更准确地判断预后、预测复发。

ObjectiveTo investigate the role of combined analysis of E2F3a and CASP8AP2 expression in prognosis evaluation in pediatric acute lymphoblastic leukemia （ALL）.MethodsThe study included 141 newly diagnosed pediatric ALL patients enrolled at the Hematology Center, Beijing Children′s Hospital, Capital Medical University between March 2008 and July 2010, including 97 boys and 44 girls（aged 1.2-15.5 years, median 5.2 years）. E2F3a and CASP8AP2 expressions were quantified in 141 children with ALL by adopting real-time quantitative polymerase chain reaction （qPCR）. Receiver operating characteristic （ROC） curve was used to find the best cut-off point to divide the patients into E2F3a or CASP8AP2 low- and high-expression groups, and the treatment outcome between the groups was compared.Cox regression was used to analyze the prognostic significance of the combined expression of E2F3a and CASP8AP2.ResultsThe estimated 5-year relapse free survival（RFS） rate, event free survival（EFS） rate and overall survival（OS） rate of patients with low-E2F3a and low-CASP8AP2 expression were （58.9±10.0）%, （56.0±9.9）% and （72.0±9.0）%, respectively.They were significantly lower than those of patients with high-E2F3a and high-CASP8AP2 expression, whose RFS, EFS and OS were （94.9±2.5）%, （93.7±2.7）% and （96.2±2.2）%, and the differences were all statistically significant（all P〈0.05）, respectively.Compared with other patients, the one with low expression of both E2F3a and CASP8AP2 had a poorer prognosis.In addition to MLL rearrangements and minimal residual disease level at the end of remission induction, low expression of both E2F3a and CASP8AP2 remained as independent prognostic factors.ConclusionLow expressions of E2F3a and CASP8AP2 predict poor prognosis in pediatric ALL.Combined assessment of E2F3a and CASP8AP2 expression could predict poor prognosis and relapse more accurately.