基于超高效液相色谱-质谱的胶质瘤患者血浆代谢组学研究

摘要

采用超高效液相色谱-四极杆-静电场轨道阱质谱(UHPLC-Q-Orbitrap HRMS)技术对胶质瘤患者和正常对照人群的血浆进行代谢轮廓分析,筛选胶质瘤代谢标志物,为其发病机制阐明和临床早期诊断提供科学依据.通过对UHPLC-Q-Orbitrap HRMS采集得到的谱图进行峰识别、峰匹配和去噪等处理后,应用主成分和正交偏最小二乘-判别分析法对代谢组学数据进行统计分析,筛选VIP＞ 1.0及P＜0.05的差异代谢物,并进一步对其诊断能力进行评价.结果显示,胶质瘤患者的血浆代谢轮廓发生明显变化,发现并鉴定得到10个差异代谢物,其中亮氨酸、缬氨酸、色氨酸、胆碱和牛磺酸在胶质瘤患者血浆中含量降低,组氨酸、柠檬酸、乳酸、肌酸和丙酮酸含量升高,与正常对照组比较具有显著性差异(P＜0.05),提示氨基酸和能量等代谢异常可能对胶质瘤的发生发展具有重要影响.此外,各差异性代谢物对胶质瘤均显示出较好的诊断能力(AUC ＞0.8),可作为潜在诊断标志物.%In this study,the ultra high performance liquid chromatography-Q exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap-HRMS) was firstly applied in the analysis of the plasma from the glioma patients and the normal control group to find the differential metabolites,which could provide the scientific evidence for clinical diagnosis and pathogenesis research.The spectra obtained by UHPLC-Q-Orbitrap HRMS were conducted to peak identification,peak matching and denoising.The data of metabolomics were statistically analyzed by using principal component analysis and orthogonal partial least-squares-discriminant analysis method to screen the differential metabolites with VIP ＞ 1.0 and P ＜ 0.05,which were investigated to further evaluate the diagnostic ability.The results showed that the plasma metabolic profiles of glioma patients were dramatically altered,and ten potential biomarkers were identified.The metabolites of leucine,valine,tryptophan,choline and taurine were significantly reduced in glioma patients,while histidine,citric acid,lactic acid,creatine and pyruvic acid were obviously increased compared with the normal controls (P ＜ 0.05),which suggested that amino acid and energy metabolism might play an important role in the development of glioma.In addition,the different metabolites showed good diagnostic ability toward gliomas (AUC ＞ 0.8),which could be used as potential diagnostic biomarkers.