目的 研究急性淋巴细胞白血病(ALL)患儿初诊骨髓样本中半胱氨酸蛋白酶8相关蛋白2 (CASP8AP2)的表达水平及其临床意义.方法 2008年4月至2009年8月,首都医科大学附属北京儿童医院收治的初发儿童ALL为研究对象,使用RQ-PCR 方法检测初诊骨髓样本中CASP8AP2的表达水平.根据ROC曲线界值将CASP8AP2水平分为高表达组和低表达组;以第33天微小残留病灶(MRD)水平分为MRD高表达和低表达组;以CASP8AP2联合第33天MRD表达水平分为高危组、中危组和低危组.分析CASP8AP2、MRD以及两者联合对预后判断的价值.结果 81例ALL患儿纳入分析,男女比例1.6:1.①复发组CASP8AP2表达显著低于非复发组,(0.45±0.31) vs (0.77±0.35),P= 0.0021;CASP8AP2高表达和低表达组的复发率分别为3.2%(2/62)和42.1%(8/19),差异有统计学意义(P<0.001),ROC曲线下面积(AUC)为0.851,95%CI:0.700~1.002.②MRD高表达组和低表达组复发率分别为23.7%(9/38)和2.3%(1/43),差异有统计学意义.ROC曲线分析显示,AUC为0.890,95%CI:0.773~1.007.③CASP8AP2-MRD低危组37例无复发,中危组2/31例(6.4%)复发,高危组8/13例(6.2%)复发,差异有统计学意义(P<0.001).Kaplan-Meier生存分析结果显示,CASP8AP2-MRD高危组的无事件生存时间及总生存时间显著低于中危组和低危组.ROC曲线分析显示,AUC为0.917,95%CI:0.837~0.997.结论 CASP8AP2的表达水平结合MRD可准确的判断儿童ALL的预后.%Objective To investigate CASP8AP2 expression in childhood acute lymphoblastic leukemia ( ALL ), its associations with clinical characteristics, and its prognostic significance for disease relapse. Methods Clinical data of patients with newly diagnosed childhood ALL were enrolled in Beijing Children's Hospital from April 2008 to August 2009. Using real-time quantitative polymerase chain reaction ( RQ-PCR ), CASP8AP2 was quantitatively detected in 81 ALL patients, ABL was detected simultaneously and used as an internal control. The average Ct value of samples obtained from five pediatric ALL patients with long-term complete continuous remission ( CCR > 5 years ) was used as a calibrator. The expression levels of CASP8AP2 were calculated by the 2 - △△Ct method and presented as fold changes compared with that of the five CCR patients. Results Eighty-one children diagnosed with ALL were included in the study. The ratio of males to females was 1.6. ①The ROC curve of CASP8AP2 was made to predict the relapse of pediatric ALL, and the area under the curve ( AUC ) was 0. 851(P<0.001). ② The expression of CASP8AP2 in the unfavorable prognosis group was significantly lower than that in the favorable prognosis group, ( 0.45 ±0. 31 ) vs ( 0.77 ± 0. 35 ) ,P = 0. 0021. ③ Using a cutoff value of 0. 4760, CASP8AP2 may be divided into high- and low-expression groups. Significantly poorer event-free survival ( EFS ) ( P < 0. 001 ) and overall survival ( OS ) ( P < 0. 001 ) were found in the low-expression group. ④ Using the expressions of CASP8AP2 and minimal residual disease ( MRD ) as bases, samples were divided into three risk groups. Differences between groups were statistically significant and indicated the capacity to predict the relapse of disease ( AUC =0. 917, P < 0. 001 ). Conclusions The expression of CASP8AP2 could be an independent prognostic factor for pediatric ALL. Joint detection of CASP8AP2 and MRD could help predict outcomes more precisely and has the potenticals to be sued as an effective means in determining prognosis, monitoring the risk of recurrence, and guiding the treatment.
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