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目的 通过尿液代谢组学分析,探讨能早期识别膀胱癌的尿液生物标志物.方法 选取膀胱癌确诊患者23例以及正常体检对照者21例,利用超高效液相色谱-高分辨率质谱联用技术(UPLC-HRMS)分析并比较膀胱癌患者与正常人尿液代谢物指纹图谱.采用正交偏最小二乘法判别法(OPLS-DA)分析早期膀胱癌患者与正常人尿液的差异代谢产物,利用UPLC-QTOF对差异产物进行结构确证.分析受试者工作特征(ROC)曲线,比较差异代谢产物在膀胱癌早期诊断中的价值.结果 尿液代谢谱分析共发现17种潜在差异代谢物,并通过结构鉴定其中5种代谢物.ROC分析最终确定2种具有潜在诊断能力的代谢物:2-辛烯二酸[OEA,FC=4.63,P＜0.01;曲线下面积(AUC) =0.787],2-羟基-3-(4-羟基-3-甲氧基苯基)丙酸(VA,FC=0.22,P＜0.01;AUC=0.762).利用两者比值则可达到更好诊断性能(OEA∶ VA,AUC=0.867).结论 基于UPLC-MS代谢组学技术对膀胱癌患者尿液代谢谱进行分析,探讨了膀胱癌发生过程中代谢变化规律,并发现2种尿液代谢标志物.

Objective Urinary metabolomic analysis was carried out to discover urinary metabolite biomarkers to assist early diagnosis of bladder cancer.Methods Ultra performance liquid chromatographyhigh-resolution mass spectrometry analysis (UPLC-HRMS) was used to analyze and compare the urinary metabolomic fingerprints from 23 patients with bladder cancer and 21 healthy controls.Data were analyzed with orthogonal partial least squares discriminant analysis (OPLS-DA) to select metabolites with differential abundance.The structure identity of potential markers was investigated by UPLC-QTOF.The receiver operating characteristic curve (ROC) was used to assess the diagnostic performance of each metabolite.Results The urinary metabolomic survey discovered 17 potential markers,5 of which were structurally identified.ROC analysis identified two metabolites with potential diagnostic value:2-Octenedioic acid (FC =4.63,P ＜ 0.01 ; AUC =0.787),Vanillactic acid (FC =0.22,P ＜ 0.01 ; AUC =0.762).The diagnostic performance could be further improved by using the ratio of these two markers (OEA∶ VA,AUC =0.867).Conclusion The Ultra performance liquid chromatography-mass spectrometry (UPLC-MS) based urinary metabolomic analysis of bladder cancer patients revealed alteration patterns of metabolites during the pathogenesis of bladder cancer,and identified 2 metabolite markers.