UPLC/Q-TOF MS联用技术对大肠癌血浆代谢组学的研究
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摘要
为从血浆中筛选可靠、特异的大肠癌生物标志物,建立无创伤性、准确的大肠癌临床诊断方法,利用超高效液相色谱和四级杆飞行时间质谱联用仪进行大肠癌血浆代谢组学分析,应用多元统计分析筛选潜在的生物标志物,利用ROC曲线验证生物标志物的诊断能力。结果表明:鉴定出的21个潜在生物标志物中,其中8个物质在癌症组上调,13个物质在癌症组下调;经ROC分析后,硫酸吲哚酚、甲酚、LysoPC(16∶0)和LysoPC(14∶0)4个物质曲线下面积大于0.9,联合诊断的灵敏度和特异度分别为98.5%和97.0%。这一研究提示硫酸吲哚酚、甲酚、LysoPC(16∶0)和LysoPC(14∶0)有可能单个或多个联合使用建立一种无创伤性的可用于大肠癌诊断方法。
The plasma metabolomics study using UPLC and quadrupole time-of-flight tandem mass spectrometry(Q-TOF MS/MS)coupled with multivariate statistics were carried out to identify potential colorectal cancer biomarkers.The diagnostic abilities of biomarkers were verified by using ROC curve analysis.An accurate clinical diagnosis method without invasion was established.21 metabolites were identified in which 8 metabolites were up-regulated while the other13 metabolites were down-regulated in colorectal cancer patients. The combination of indoxyl sulfate,cresol,lysoPC(16∶0)and lysoPC(14∶0)was able to discriminate colorectal cancer patients from normal healthy controls with sensitivity(98.5%)and specificity(97.0%).The single or multiple combinations of indoxyl sulfate,cresol,lysoPC(16∶0)and lysoPC(14∶0)in plasma could give a noninvasive and accurate diagnosis for colorectal cancer.
The plasma metabolomics study using UPLC and quadrupole time-of-flight tandem mass spectrometry(Q-TOF MS/MS)coupled with multivariate statistics were carried out to identify potential colorectal cancer biomarkers.The diagnostic abilities of biomarkers were verified by using ROC curve analysis.An accurate clinical diagnosis method without invasion was established.21 metabolites were identified in which 8 metabolites were up-regulated while the other13 metabolites were down-regulated in colorectal cancer patients. The combination of indoxyl sulfate,cresol,lysoPC(16∶0)and lysoPC(14∶0)was able to discriminate colorectal cancer patients from normal healthy controls with sensitivity(98.5%)and specificity(97.0%).The single or multiple combinations of indoxyl sulfate,cresol,lysoPC(16∶0)and lysoPC(14∶0)in plasma could give a noninvasive and accurate diagnosis for colorectal cancer.
引文
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[3]SIEGEL R L,MILLER K D,JEMAL A.Cancer statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.
[4]CUNNINGHAM D,ATKIN W,LENZ H J,et al.Colorectal cancer[J].Lancet,2010,375(9719):1030-1047.
[5]HOL L,VAN LEERDAM M E,VAN BALLEGOOIJEN M,et al.Screening for colorectal cancer:randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy[J].Gut,2010,59(1):62-68.
[6]ZAUBER A G,WINAWER S J,O'BRIEN M J,et al.Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths[J].N Engl J Med,2012,366(8):687-696.
[7]POX C P,ALTENHOFEN L,BRENNER H,et al.Efficacy of a nationwide screening colonoscopy program for colorectal cancer[J].Gastroenterology,2012,142(7):1460-1467.
[8]SCHOLEFIELD J H,MOSS S M,MANGHAM C M,et al.Nottingham trial of faecal occult blood testing for colorectal cancer:a 20-year follow-up[J].Gut,2012,61(7):1036-1040.
[9]NISHIHARA R,WU K,LOCHHEAD P,et al.Long-term colorectal-cancer incidence and mortality after lower endoscopy[J].The New England Journal of Medicine,2013,369(12):1095-1105.
[10]VAN ROSSUM L G,VAN RIJN A F,LAHEIJ R J,et al.Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population[J].Gastroenterology,2008,135(1):82-90.
[11]NISHIUMI S,KOBAYASHI T,IKEDA A,et al.A novel serum metabolomics-based diagnostic approach for colorectal cancer[J].PloS ONE,2012,7(7):e40459.
[12]BOSCH L J,CARVALHO B,FIJNEMAN R J,et al.Molecular tests for colorectal cancer screening[J].Clin Colorectal Cancer,2011,10(1):8-23.
[13]IMPERIALE T F,RANSOHOFF D F,ITZKOWITZ S H,et al.Multitarget stool DNA testing for colorectalcancer screening[J].N Engl J Med,2014,370(14):1287-1297.
[14]夏冰洋,马亚萍,李楠楠,等.超高效液相色谱-串联质谱法同时测定人尿中5种甾体激素[J].扬州大学学报(农业与生命科学版),2016,37(3):30-36.
[15]MAL M,KOH P K,CHEAH P Y,et al.Metabotyping of human colorectal cancer using two-dimensional gas chromatography mass spectrometry[J].Anal Bioanal Chem,2012,403(2):483-493.
[16]GAO P,ZHOU C,ZHAO L,et al.Tissue amino acid profile could be used to differentiate advanced adenoma from colorectal cancer[J].J Pharm Biomed Anal,2016,118(3):49-55.
[17]ZHU J,DJUKOVIC D,DENG L,et al.Colorectal cancer detection using targeted serum metabolic profiling[J].J Proteome Res,2014,13(9):4120-4130.
[18]TAN B,QIU Y,ZOU X,et al.Metabonomics identifies serum metabolite markers of colorectal cancer[J].J Proteome Res,2013,12(6):3000-3009.
[19]WILLIAMS M D,ZHANG X,PARK J J,et al.Characterizing metabolic changes in human colorectal cancer[J].Analytical&Bioanalytical Chemistry,2015,407(16):4581-4595.
[20]QIU Y,CAI G,SU M,et al.Urinary metabonomic study on colorectal cancer[J].J Proteome Res,2010,9(3):1627-1634.
[21]CHENG Y,XIE G,CHEN T,et al.Distinct urinary metabolic profile of human colorectal cancer[J].J Proteome Res,2012,11(2):1354-1363.
[22]CROSS A J,MOORE S C,BOCA S,et al.A prospective study of serum metabolites and colorectal cancer risk[J].Cancer,2014,120(19):3049-3057.
[23]BERNSTEIN C,HOLUBEC H,BHATTACHARYYA A K,et al.Carcinogenicity of deoxycholate,a secondary bile acid[J].Arch Toxicol,2011,85(8):863-871.
[24]NAGENGAST F M,GRUBBEN M J,VAN MUNSTER I P.Role of bile acids in colorectal carcinogenesis[J].Eur J Cancer,1995,31A(7/8):1067-1070.
[25]陈大卫,范晨雨,鲁茂林,等.广西巴马地区人群肠道菌群的影响因素研究[J].扬州大学学报(农业与生命科学版),2017,38(4):18-24.