血清神经元特异性烯醇化酶和尿香草扁桃酸与神经母细胞瘤临床病理特征的相关性

Correlation of neuron-specific enolase and vanillylmandelic acid with clinico pathological features of neuroblastomas

目的:分析神经母细胞瘤(neuroblastoma,NB)患儿治疗前血清神经元特异性烯醇化酶(neuron-specific enolase,NSE)和尿香草扁桃酸(vanillymandelic acid,VMA)的水平,比较二者与NB临床病理特征的相关性以及二者预测高危组患儿的能力,为更好地诊断和评估病情提供依据。方法:收集2011年9月至2019年9月天津医科大学肿瘤医院确诊的155例NB患儿的临床病理资料。回顾性分析不同临床特征的患儿血清NSE和尿VMA水平,包括年龄、性别、肿瘤体积及部位、病理类型、INSS分期、危险度分组、是否转移、MYCN基因扩增及有无IDRFs情况。采用非参数秩和检验比较组间差异,P<0.05为差异具有统计学意义。为比较血清NSE和尿VMA在高危组患儿中的诊断价值,绘制ROC曲线,建立预测模型,比较二者鉴别高危组患儿的准确性。结果:109例患儿检测尿VMA,其中阴性61例,阳性48例,阳性率44.0%。152例患儿检测血清NSE,其中阴性2例,阳性150例,阳性率98.7%。血清NSE和尿VMA水平在INSS 4期、COG高危组、伴有转移和有IDRFs的患儿中均显著增高(P<0.05)。血清NSE在肿瘤部位、肿瘤体积和病理类型不同的患儿中具有显著性差异;肿瘤体积>500 cm3、INPC预后不良,病理类型为NB,原发灶位于腹膜后的患儿,血清NSE水平显著高于其他组(P<0.001)。ROC曲线结果显示血清NSE鉴别高危组患儿的界值为98.50 ng/mL,曲线下面积AUC为0.943(95%CI:0.906~0.991)。尿VMA鉴别高危组患儿的界值为62.28μmoL/24 h,AUC为0.791(95%CI:0.705~0.878)。联合二者鉴别高危组患儿,AUC为0.948(95%CI:0.900~0.997)。结论:与尿VMA相比,血清NSE与更多的NB临床特征相关,可以更全面地辅助诊断疾病及评估病情。在高危组患儿中,血清NSE和尿VMA水平均显著增高。NSE鉴别高危组患儿的准确性、灵敏度和特异度均高于尿VMA,二者联合检测并不能提高诊断的准确性。

Objective:To summarize and analyze serum neuron-specific enolase(NSE)and urine vanillylmandelic acid(VMA)levels in children with neuroblastoma before treatment by correlating these levels with clinicopathological features of neuroblastomas,establishing their ability to predict high-risk children,and finally,providing a basis for better diagnosis and assessment of neuroblastomas.Methods:Clinicopathological data of 155 children with a confirmed diagnosis of neuroblastoma at Tianjin Medical University Cancer Institute and Hospital from September 30,2011 to September 11,2019 were collected.A retrospective analysis was performed to analyze serum NSE and urine VMA levels in children with different clinical features such as age,gender,tumor size and location,pathological pattern,staging,risk grouping,metastasis,MYCN gene amplification,and image-defined risk factors(IDRFs).Differences between groups were compared using a nonparametric rank-sum test.A P-value<0.05 was considered statistically significant.Receiver operating characteristic(ROC)curves and prediction models were used to determine the accuracy of serum NSE and urine VMA in identifying high-risk children,thereby establishing the diagnostic value of these indicators.Results:Of 109 children tested for urine VMA,61 and 48 children had negative and positive results,respectively,resulting in a positive rate of 44.0%.Of 152 children tested for serum NSE,2 and 150 children had negative and positive results,respectively,suggesting a positive rate of 98.7%.Serum NSE and urine VMA levels were significantly increased in children with an INSS stage 4 classification,a COG high-risk grouping,metastases,and with presence of IDRFs(P<0.05).The serum NSE level was also significantly different in children depending on the varying tumor sites,gross tumor volumes,and pathological patterns.Specifically,the NSE level was significantly higher in children with tumors>500 cm3,an unfavorable prognosis based on the INPC,a pathological pattern of neuroblastoma,and a retroperitoneal primary tumor focus than in children of other groups(P<0.001).The ROC curves revealed that a serum NSE cut-off level of 98.50 ng/mL with an area under the curve(AUC)of 0.943(95%confidence interval[CI],0.906-0.991)and a urine VMA cut-off level of 62.28μmol/24 h with an AUC of 0.791(95%CI,0.705-0.878)could identify high-risk children.When the two indicators were combined to identify high-risk children,the AUC was 0.948(95%CI,0.900-0.997).Conclusions:Compared with urine VMA,serum NSE levels correlated with more clinical features of neuroblastomas;thus,serum NSE could better assist in the diagnosis and evaluation of the disease by providing more comprehensive results.While both serum NSE and urine VMA levels are significantly higher in high-risk children,the accuracy,sensitivity,and specificity of serum NSE are all higher than those of urine VMA in identifying high-risk children.A combination of the two indicators does not improve diagnostic accuracy.