摘要
目的:探讨趋化因子受体7(CCR7)与T细胞免疫球蛋白粘液素-3(Tim-3)在儿童急性淋巴细胞白血病(ALL)中的表达及其联合检测对预后评估的价值。方法:选取本院2007年1月至2017年1月期间收治的初治ALL患者86例,采用流式细胞仪检测入组对象的骨髓分离细胞中CCR7、Tim-3表达水平,根据随访结果分为复发组和非复发组,比较2组CCR7、Tim-3表达差异,分析CCR7、Tim-3的表达与ALL患者临床病理特征的相关性,采用ROC曲线评价CCR7、Tim-3对初治ALL患者的评估预测价值,分析ALL患者CCR7、Tim-3表达与预后的关系。结果:复发组CCR7与Tim-3表达水平明显高于非复发组(P<0.05);CCR7诊断的临界值为45.97%,其对应的灵敏度为66.7%,特异度为84.5%,ROC曲线下面积分别为0.798(95 CI 0.777-0.939);Tim-3诊断的临界值为53.54%,其对应的灵敏度为73.3%,特异度为80.3%,ROC曲线下面积分别为0.806(95 CI 0.792-0.947);联合诊断ROC曲线下面积分别为0.895(95 CI 0.914-0.996),对应的灵敏度86.6%,特异度78.9%(P<0.05);CCR7、Tim-3表达与年龄、性别、血红蛋白浓度、白细胞数、骨髓中原始细胞数、血小板计数、中枢神经系统侵袭、细胞遗传学融合基因无明显相关性(P>0.05);CCR7、Tim-3高表达患者髓外浸润率明显高于低表达组(P<0.05);T-ALL患者Tim-3高表达率(76.9%)明显高于B-ALL患者Tim-3高表达率(45.2%)(P<0.05);CCR7≥45.97%及<45.97%患者中位OS时间分别为9.3个月、13.6个月(P=0.004)。Tim-3≥53.54%及Tim-3<53.54%患者的中位OS时间分别为9.1个月、13.6个月(P=0.001)。COX多因素回归分析结果显示,CCR7(HR=1.024,95 CI1.000-1.049)及Tim-3(HR=1.879,95 CI 1.183-2.985)水平为影响ALL患者OS的独立危险因素(P<0.05)。结论:急性淋巴细胞白血病儿童初诊骨髓细胞中CCR7、Tim-3表达对于疾病预后具有良好的预测价值,二者联合检测能够提升检测的灵敏度,CCR7、Tim-3高表达与OS密切相关,可以作为评估ALL预后的潜在指标。
Objective:To analyze the expression of CCR7 and Tim-3 in childhood patients with acute lymphoblastic leukemia(ALL)and their predictive value for prognosis.Methods:Eighty-six newly diagnosed ALL childhood patients from January 2007 to January 2017 treated in our hospital were selected.The expression level of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients were detected by flow cytometry,all the patients were divided into the recurrence group and non-recurrence group according to the follow-up results,the differences in the expressions of CCR7,Tim-3 between the two groups were compared.The correlation between the expression of CCR7,Tim-3 and the clinicopathologic features of ALL patients were analyzed,the predictive value of CCR7 and Tim-3 for the prognosis of newly ALL patients were evaluated by ROC curve,and the relationship between serum CCR7,Tim-3 and prognosis were analyzed.Results:The expression levels of CCR7 and Tim-3 in recurrence group were significantly higher than those in non-recurrence group(P<0.05).The critical value of CCR7 for diagnosis of recurrence was 45.97%,the sensitivity was 66.1%,the specificity was the 84.5%and the area under ROC curve(AUC)was 0.798(95 CI 0.777-0.939).The critical value of Tim-3 for diagnosis of recurrence was 53.54%,the sensitivity was 73.3%,the specificity was the80.3%and the AUC was 0.806(95 CI 0.792-0.947).The AUC of the combined detection of CCR7 and Tim-3 was0.895(95 CI 0.914-0.996),sensitivity 86.6%,specificity 78.9%(P<0.05);There was no significant correlation between CCR7,Tim-3 expression and age,sex,hemoglobin concentration,number of white blood cells,bone marrow blasts,platelets,central nervous system invasion,fusion gene(P>0.05).The exogenous infiltration rate of patients with high expression of CCR7 and Tim-3 was significantly higher than those in low expression group(P<0.05).The high expression rate 16.9%of Tim-3 in patients with T-ALL was significantly higher than that of B-ALL patients with Tim-3 high expression rate 45.2%(P<0.05).The median OS
作者
马丽
蒯文霞
祁海啸
张荣荣
袁玉芳
赵继欧
MA Li;KUAI Wen-Xia;QI Hai-Xiao;ZHANG Rong;YUAN Yu-Fang;ZHAO Ji-Ou(Department of Pediatrics,Huai'an First Hospital Affiliated to Nanjing Medical University,Huai'an 223300,Jiangsu Province,China)
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2019年第6期1728-1735,共8页
Journal of Experimental Hematology
