CAJ | 학술논문

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.
목적 통과뇨액대사조학분석,탐토능조기식별방광암적뇨액생물표지물.방법 선취방광암학진환자23례이급정상체검대조자21례,이용초고효액상색보-고분변솔질보련용기술(UPLC-HRMS)분석병비교방광암환자여정상인뇨액대사물지문도보.채용정교편최소이승법판별법(OPLS-DA)분석조기방광암환자여정상인뇨액적차이대사산물,이용UPLC-QTOF대차이산물진행결구학증.분석수시자공작특정(ROC)곡선,비교차이대사산물재방광암조기진단중적개치.결과 뇨액대사보분석공발현17충잠재차이대사물,병통과결구감정기중5충대사물.ROC분석최종학정2충구유잠재진단능력적대사물:2-신희이산[OEA,FC=4.63,P＜0.01;곡선하면적(AUC) =0.787],2-간기-3-(4-간기-3-갑양기분기)병산(VA,FC=0.22,P＜0.01;AUC=0.762).이용량자비치칙가체도경호진단성능(OEA∶ VA,AUC=0.867).결론 기우UPLC-MS대사조학기술대방광암환자뇨액대사보진행분석,탐토료방광암발생과정중대사변화규률,병발현2충뇨액대사표지물.
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.