神经母细胞瘤中TrkA基因三种异构体表达及其临床意义

Expression of TrkA Splicing Isoforms in Neuroblastoma and Its Clinical Significance

目的:探讨神经母细胞瘤(NB)中TrkA基因三种异构体的表达及其临床意义。方法:回顾性分析随访资料较完整的首诊为NB的患儿39例。采用SYRB Green Ⅰ荧光定量PCR方法检测39例NB手术切除标本中TrkA异构体mRNA的表达。t检验比较不同临床分期中TrkA异构体的表达差异。按首次就诊时临床资料(年龄、性别、原发部位、转移部位、临床分期),TrkA Ⅰ/Ⅱ与TrkAⅢ的表达比值等因素进行分组。Kaplan-Meier法计算5年生存率,单因素分析用Kaplan-Meier生存曲线比较组间生存率,显著性检验采用Log-Rank法。COX回归模型进行多因素分析。结果:TrkA Ⅰ/Ⅱ的表达在低分期组明显大于高分期组(P<0.01),而TrkAⅢ的表达在低分期组明显低于高分期组(P<0.01),TrkA Ⅰ/Ⅱ与TrkAⅢ的表达比值在低分期组明显高于高分期组(P<0.01)。单因素分析发现年龄>1岁、腹部原发、骨骼转移、Evans第Ⅲ/Ⅳ期、TrkA Ⅰ/Ⅱ与TrkAⅢ表达比值较低组别的5年生存率,明显低于其对照组。性别对生存率无影响。COX模型多因素分析显示骨骼转移、TrkA Ⅰ/Ⅱ与TrkAⅢ表达比值低对5年生存率产生不良影响。结论:TrkA Ⅰ/Ⅱ高表达示NB患者后良好,TrkAⅢ高表达示NB患者预后较差。早期对肿瘤行TrkA基因检测及骨骼扫描,对NB患者预后预测具有重要意义。

Objective： To study the expression and clinical significance of TrkA splicing isoforms in human neuroblastoma. Methods： Data from 39 patients with neuroblastoma were studied retrospectively. Expression of TrkA mRNA isoforms was detected by SYBR Green I fluorescence quantitative PCR in the 39 cases. The differences in TrkA splicing isoform expression in different clinical stages were tested with t-test. Kaplan-Meier methods were used to estimate the 5-year survival rate. For univariate analysis, Kaplan-Meier survival analysis was used to establish the 5-year survival rate from the time of diagnosis, and log-rank statistical analysis was used to test the significance in the differences in 5-year survival rates between subgroups of patients. Analysis of multiple variables was performed using the COX regression method. The factors examined included clinical variables （age, sex, primary site of tumor, metastatic sites, and stages）, ratio between TrkA Ⅰ/Ⅱ expression and TrkA Ⅲ expression. Results： TrkA Ⅰ/Ⅱ expression in tumors of a lower stage was significantly higher than in tumors of a higher stage （P〈0.01）, while the expression of TrkA Ⅲ in lower stage tumors was significantly lower than in the higher stage tumors （P〈0.01）. Univariate analysis showed that the 5-year survival rate of patients with age 〉1 year, ab- dominal origin, bone metastasis, Evans Ⅲ-Ⅳ stage, lower TrkA Ⅰ/Ⅱ to TrkAlll ratio was significantly lower than that of the control group. Multivariate analysis demonstrated that only the bone metastasis and lower TrkA Ⅰ/Ⅱ to TrkA Ⅲ ratio had negative effects on the 5-year survival rate of patients with neuroblastoma. Condusion： TrkA Ⅰ/Ⅱ was highly expressed in NB with good prognosis, while TrkA Ⅲ was highly expressed in NB with poor prognosis. Early detection of TrkA gene expression and bone scanning are important for evaluation of the outcomes of neuroblastoma.