基于非靶标代谢组学的转移性神经母细胞瘤患儿血浆代谢特征研究  

Plasma metabolic characteristics of children with metastatic neuroblastoma based on non-target metabolomics

作　　者：杜邦 孙萌[1] 秦雪怡 郜晶 秦红[2] 王焕民[2] 张现伟 周崇臣 张万存 Du Bang;Sun Meng;Qin Xueyi;Gao Jing;Qin Hong;Wang Huanmin;Zhang Xianwei;Zhou Chongchen;Zhang Wancun(Zhengzhou Key Laboratory of Precision Diagnosis and Treatment of Pediatric Malignant Tumors,Children's Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,China;Department of Surgical Oncology,Beijing Children's Hospital,Capital Medical University,Beijing 100045,China)

机构地区：[1]郑州大学附属儿童医院,郑州市儿童恶性肿瘤精准诊疗重点实验室,郑州450018 [2]首都医科大学附属北京儿童医院肿瘤外科,北京100045

出　　处：《中华小儿外科杂志》2025年第2期106-113,共8页Chinese Journal of Pediatric Surgery

基　　金：国家自然科学基金(32201237);河南省科技项目(232102311135、222102310270、222102310109);河南省医学科技计划项目(LHGJ20210618,LHGJ20220767)。

摘　　要：目的研究转移性神经母细胞瘤(metastatic neuroblastoma,MNB)与非转移性神经母细胞瘤(non-MNB)患儿血浆代谢组学的差异。方法采用高效液相色谱-质谱联用技术对MNB患儿(53例)和non-MNB患儿(29例)血浆代谢组学数据进行采集,使用MetaboAnalyst 5.0软件对代谢组学数据进行分析,基于主成分分析、偏最小二乘法判别分析进行建模和多标准评价体系寻找两组间差异代谢物,最终利用富集分析筛选异常表达代谢通路。结果基于MNB与non-MNB患儿血浆代谢组学数据,依据变量权重值(variableimportant in projection,VIP)>1、|log_(2)差异倍数|>1且P<0.05,共筛选出30种差异代谢物,其中MNB中上调的代谢物有4种,如Spiroxamine,Phytanal等,下调的代谢物有26种,如LysoPC(16∶0),LysoPC[18∶2(9Z,12Z)],SM(d18∶2/16∶0)等。基于小分子通路数据库富集分析共筛选出11条差异代谢通路,如心磷脂生物合成、磷脂酰乙醇胺生物合成、磷脂酰胆碱生物合成、儿茶酚胺生物合成等。结论与non-MNB患儿相比,MNB患儿的血浆代谢存在磷脂、儿茶酚胺合成代谢通路,可为NB的临床诊断和药物治疗提供新的思路。ObjectiveTo investigate the differences in plasma metabolome between children with metastatic neuroblastoma(MNB)and non-metastatic neuroblastoma(non-MNB).MethodsThe plasma metabolome data of children with MNB(n=53)and non-MNB(n=29)were detected using high performance liquid chromatography-mass spectrometry.MetaboAnalyst 5.0 was used to analyze the metabolomics data.The principal component analysis,partial least square discriminant analysis and multi-criteria evaluation system were used to identify differentially expressed metabolites between the two groups.Gene set enrichment analysis was used to screen the enriched metabolic pathways.ResultsBased on the plasma metabolomics data of MNB and non-MNB children,30 differentially expressed metabolites with variable importance in projection(VIP)>1,|log_(2)fold change|>1,and P<0.05 were identified.Among them,4 metabolites were up-regulated in MNB,such as Spiroxamine,Phytanal,Deoxycytosine,and 26 metabolites were down-regulated,such as LysoPC(16∶0),LysoPC[18∶2(9Z,12Z)],and SM(d18∶2/16∶0).Based on the small molecule pathway database enrichment analysis,a total of 11 pathways significantly enriched in differentially expressed metabolites were identified,including cardiolipin biosynthesis,phosphatidylethanolamine biosynthesis,phosphatidylcholine biosynthesis,catecholamine biosynthesis and other metabolic pathways.ConclusionsThe discovery of phospholipid and catecholamine synthesis metabolic pathways contributes to identifying important biomarkers and therapeutic targets in NB,providing new perspectives for the clinical diagnosis and pharmacological treatment of NB.

关 键 词：神经母细胞瘤 转移 代谢组学 代谢通路 

分 类 号：R739.4[医药卫生—肿瘤]