MYCN扩增型神经母细胞瘤潜在预后生物标志物的综合性分析

A comprehensive analysis of potential prognostic biomarkers for MYCN-amplified neuroblastoma

目的分析比较MYCN扩增型神经母细胞瘤(NB)和MYCN非扩增型NB表达mRNA的差别,筛选具有预测MYCN扩增型NB预后功能的基因并分析其对预后的预测价值.方法从TARGET数据库获得NB转录组数据和患儿临床资料,根据有无MYCN扩增分为MYCN扩增组(n=33)和MYCN非扩增组(n=121),对两组mRNA进行差异分析,得到差异表达基因(DEGs).采用GO和KEGG数据库分析DEGs的主要功能.采用Cox比例风险回归模型分析影响MYCN扩增组NB预后的基因,根据风险评分的中位值分为高风险组(n=77)和低风险组(n=77),采用生存分析法比较两组生存率,ROC曲线分析风险评分对MYCN扩增型NB患儿预后的预测价值.结果共筛选出582个DEGs,这些DEGs参与了核糖体组成、细胞黏附蛋白的表达以及膜蛋白受体活动等重要生物功能.多因素Cox回归模型分析结果显示FLVCR2、SCN7A、PRSS12、NTRK1、XAGE1A基因对MYCN扩增组NB患儿预后具有显著性影响(均P<0.05).生存分析发现,高风险组的总生存率低于低风险组(P<0.05).ROC分析显示,风险评分对MYCN扩增组NB患儿预后有预测价值(P<0.05),曲线下面积为0.729,最佳截断值为1.316,灵敏度为53.2%,特异度为84.4%.结论FLVCR2、SCN7A、PRSS12、NTRK1、XAGE1A基因的mRNA可作为预测MYCN扩增型NB预后的生物标志物,有助于细化临床危险分层.

Objective To study the differentially expressed mRNAs between MYCN-amplified neuroblastoma(NB)and non-amplified NB,to screen out the genes which can be used to predict the prognosis of MYCN-amplified NB,and to analyze their value in predicting prognosis.Methods NB transcriptome data and the clinical data of children were obtained from the TARGET database.According to the presence or absence of MYCN amplification,the children were divided into two groups:MYCN amplification(n=33)and non-MYCN amplification(n=121).The expression of mRNAs was compared between the two groups to obtain differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genome(KEGG)analysis was performed to investigate the main functions of DEGs.The Cox proportional-hazards regression model analysis was used to investigate the genes influencing the prognosis of MYCN-amplified NB.The children were divided into a high-risk group(n=77)and a low-risk group(n=77)based on the median of risk score.A survival analysis was used to compare survival rate between the two groups.The receiver operating characteristic(ROC)curve was used to investigate the value of risk score in predicting the prognosis of children with MYCN-amplified NB.Results A total of 582 DEGs were screened out,and they were involved in important biological functions such as ribosome composition, expression of cell adhesion molecules, andactivity of membrane receptor protein. The multivariate Cox regression model analysis showed that FLVCR2, SCN7A,PRSS12, NTRK1, and XAGE1A genes had a marked influence on the prognosis of the children with NB in the MYCNamplification group (P<0.05). The survival analysis showed that the high-risk group had a significantly lower overallsurvival rate than the low-risk group (P<0.05). The ROC curve analysis showed that risk score had a certain value inpredicting the prognosis of the children with NB in the MYCN amplification group (P<0.05), with an area under theROC curve of 0.729, an optimal cut-off value of 1.316, a sensitivity of 53.2%, and a specificity of 84.4%. ConclusionsThe mRNA expression of FLVCR2, SCN7A, PRSS12, NTRK1, and XAGE1A genes can be used as biomarkers topredict the prognosis of MYCN-amplified NB, which can help to refine clinical risk stratification.