无MYCN基因扩增的儿童神经母细胞瘤预后列线图构建

Construction of prognostic nomogram for childhood neuroblastoma without MYCN gene amplification

目的分析无MYCN基因扩增的儿童神经母细胞瘤预后因素,并构建及评价列线图预后模型。方法回顾性分析美国国家癌症研究所TARGET数据库获得1986-2012年诊断为无MYCN基因扩增的儿童神经母细胞瘤596例,按照7∶3随机分为建模组(420例)和验证组(176例),应用最小绝对值选择与收缩算子(LASSO)回归、单因素及多因素COX比例风险回归分析筛选独立的预后因子,并构建可以预测3、5年总体生存率(OS)的列线图模型。通过绘制受试者工作特征曲线(ROC)计算曲线下面积(AUC)及C指数评价模型区分度,通过绘制校准曲线评价模型一致性。结果LASSO回归筛选出年龄、DNA倍性、国际神经母细胞瘤分期系统(ISSN)3个预后因子,单因素及多因素COX比例风险回归进一步明确3个因子均为独立的预后因子,基于这些预后因子构建了预测3、5年OS的列线图模型。列线图C指数在建模组和验证组分别为0.755和0.732,ROC显示列线图在预测建模组3、5年OS的AUC分别为0.780和0.806,验证组3、5年OS的AUC分别为0.756和0.777。校准曲线显示模型预测3、5年OS与实际生存率一致性良好。结论年龄、DNA倍性、ISSN分期的儿童神经母细胞瘤的独立预后因子,列线图模型区分度及一致性良好,可以准确预测患儿预后。

Objective To analyze the prognostic factors of childhood neuroblastoma without MYCN gene amplification,and to construct and evaluate the nomogram prognostic model.Methods A total of 596 cases of childhood neuroblastoma without MYCN gene amplification obtained from the TARGET database in US National Cancer Institute during 1986-2012 were retrospectively analyzed.They were randomly divided into the modeling group and validation group according to 7∶3.The independent prognostic factors were screened by the LASSO regression,univariate and multivariate Cox regression analysis,and the nomogram model for predicting the overall survival rate(OS)of 3 and 5 years was constructed.The area under the curve(AUC)and C-index were calculated by drawing the receiver operating characteristic(ROC)curve to evaluate the model discrimination,and the consistency of the model was evaluated by drawing the calibration curve.Results The LASSO regression screened the three prognostic factors:age,DNA ploidy and INSS stage system.The univariate and multivariate Cox regression further confirmed that the three factors were the independent prognostic factors.Based on these prognostic factors,a nomogram model for predicting 3-year and 5-year OS was constructed.The C-index of nomogram in the modeling group and validation group were 0.755 and 0.732 respectively.The ROC curve showed that AUC of nomogram in predicting the 3-year and 5-year OS in the modeling group were 0.780 and 0.806 respectively,and which in the validation group were 0.756 and 0.777 respectively.The calibration curve showed that the 3-year and 5-year overall survival rate predicted by the model was in good agreement with the actual survival rate.Conclusion Age,DNA ploidy and stage are the independent prognostic factors of childhood neuroblastoma without MYCN gene amplification.The nomogram model has good discrimination and consistency,and could accurately predict the prognosis of children patients.