CAJ | 학술논문

目的检测胰腺癌患者与健康者血清的代谢组学,筛选能够鉴别胰腺癌与健康者的差异代谢物,寻找潜在的胰腺癌早期诊断标志物.方法采用病例对照成组分析方法,以病理诊断为胰腺导管腺癌患者作为病例组,健康人群为对照组.应用高效液相色谱单级四级杆飞行时间串联质谱联用仪检测胰腺癌及健康者的血清代谢组学.通过单维及多维统计方法分析两组间代谢组学的差异,根据分子质量、代谢产物数据库和质谱/质谱(MS/MS)信息筛选差异代谢物.通过差异代谢物的受试者工作特征曲线下面积(AUC)评价它们鉴别胰腺癌及健康者的价值.结果共纳入胰腺导管腺癌患者及健康者各54例,年龄及性别相匹配.最终筛选出12种差异代谢物,其中胰腺癌患者血清中羟基花生四烯酸(HETE)、苯丙氨酸、乙酰肉碱、亚油酸、棕榈酰肉碱、亚油醇肉碱、尿嘧啶脱氧核苷酸(dUMP)和甘氨鹅脱氧胆酸8种代谢产物水平显著高于健康者;溶血磷脂酰胆碱[LysoPC(18∶ 0)]、LysoPC(P-16∶0)、溶血磷脂酸[LPA(182/0∶0)]、LysoPC(14∶0)4种代谢产物水平显著低于健康者(P值均＜0.05).HETE、LysoPC(18∶0)、苯丙氨酸、LPA(18∶ 2/0∶ 0)、dUMP的AUC分别为0.98、0.96、0.92、0.91,均大于CA19-9的AUC(0.90).结论胰腺导管腺癌患者及健康者的血清代谢组共筛选出12种差异代谢物,其中HETE、LysoPC(18∶0)、苯丙氨酸、LPA(18∶ 2/0∶0)、dUMP有可能是潜在的诊断标志物.
목적 검측이선암환자여건강자혈청적대사조학,사선능구감별이선암여건강자적차이대사물,심조잠재적이선암조기진단표지물.방법 채용병례대조성조분석방법,이병리진단위이선도관선암환자작위병례조,건강인군위대조조.응용고효액상색보단급사급간비행시간천련질보련용의검측이선암급건강자적혈청대사조학.통과단유급다유통계방법분석량조간대사조학적차이,근거분자질량、대사산물수거고화질보/질보(MS/MS)신식사선차이대사물.통과차이대사물적수시자공작특정곡선하면적(AUC)평개타문감별이선암급건강자적개치.결과 공납입이선도관선암환자급건강자각54례,년령급성별상필배.최종사선출12충차이대사물,기중이선암환자혈청중간기화생사희산(HETE)、분병안산、을선육감、아유산、종려선육감、아유순육감、뇨밀정탈양핵감산(dUMP)화감안아탈양담산8충대사산물수평현저고우건강자;용혈린지선담감[LysoPC(18∶ 0)]、LysoPC(P-16∶0)、용혈린지산[LPA(182/0∶0)]、LysoPC(14∶0)4충대사산물수평현저저우건강자(P치균＜0.05).HETE、LysoPC(18∶0)、분병안산、LPA(18∶ 2/0∶ 0)、dUMP적AUC분별위0.98、0.96、0.92、0.91,균대우CA19-9적AUC(0.90).결론 이선도관선암환자급건강자적혈청대사조공사선출12충차이대사물,기중HETE、LysoPC(18∶0)、분병안산、LPA(18∶ 2/0∶0)、dUMP유가능시잠재적진단표지물.
Objective To investigate the overall serum metabolic differences between pancreatic cancer and healthy controls and screen the different metabolites as potential diagnostic marker for early diagnosis of pancreatic cancer.Methods Case control group analysis method was used,and patients with pathological diagnosis of pancreatic ductal adenocarcinoma were considered as case group,and healthy subjects were considered as control group.UHPLC/Q-TOF MS-based metabonomics techniques were applied to analyze the difference in serum metabolites in the two groups with multivariate and univariate statistical method,and the different metabolites were screened and identified in accordance with the molecular weight,metabolites databases and MS/MS information.The diagnostic discrimination of the different metabolites was evaluated by ROC curve.Results In this study,there were 54 patients with pathological diagnosis of pancreatic ductal adenocarcinoma and 54 age and sex matched healthy controls.There were 12 kinds of different serum metabolits in the final screening and identification in the two groups.The level of hydroxy-arachidonic acid,phenylalanine,acetylcarnitine,linoleic acid,palmitoylcarnitine,linoleyl carnitine,and uracil deoxynucleotide and glycocholic chenodeoxycholic acid in serum of pancreatic cancer patients were higher than those in the controls (P ＜ 0.05).Serum LysoPC (18∶ 0),LysoPC (P-16∶ 0),LPA (18 ∶ 2/0∶ 0),LysoPC (14∶ 0) in patients with pancreatic ductal adenocarcinoma were lower than those in the controls (P ＜ 0.05).The AUC of HETE,LysoPC (18∶ 0),phenylalanine,LPA (18∶ 2/0∶ 0),dUMP was 0.98,0.96,0.92,0.91,respectively,which were significantly higher than that of CA19-9 (0.90).Conclusions Twelve kinds of different serum metabolits are screened and identified between pancreatic ductal adenocarcinoma patients and healthy subjects,and HETE,LysoPC (18∶ 0),phenylalanine,LPA(18∶ 2/0∶ 0),dUMP may be potential markers for diagnosis of pancreatic cancer.