1.广西大学 医学院,广西 南宁 530004
2.湖北民族大学 风湿性疾病发生与干预湖北省重点实验室, 湖北 恩施 445000
3.广西壮族自治区人民医院消化内科,广西 南宁 530021
黄宗声,硕士,初级医师,研究方向:消化内科,E-mail:459091314@qq.com
张淇淞,博士,助理教授,研究方向:代谢组学与药物分析,E-mail:zhangqisong@gxu.edu.cn
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杨珊伊,陈鸿炜,周海琳等.基于超高效液相色谱-串联高分辨质谱的血清代谢组学用于探索区分结直肠腺瘤和结直肠癌的生物标志物[J].分析测试学报,2023,42(02):173-180.
YANG Shan-yi,CHEN Hong-wei,ZHOU Hai-lin,et al.Exploration on Biomarkers for Discrimination of Colorectal Adenoma and Cancer by UHPLC-HRMS-based Serum Metabolomics[J].Journal of Instrumental Analysis,2023,42(02):173-180.
杨珊伊,陈鸿炜,周海琳等.基于超高效液相色谱-串联高分辨质谱的血清代谢组学用于探索区分结直肠腺瘤和结直肠癌的生物标志物[J].分析测试学报,2023,42(02):173-180. DOI: 10.19969/j.fxcsxb.22092103.
YANG Shan-yi,CHEN Hong-wei,ZHOU Hai-lin,et al.Exploration on Biomarkers for Discrimination of Colorectal Adenoma and Cancer by UHPLC-HRMS-based Serum Metabolomics[J].Journal of Instrumental Analysis,2023,42(02):173-180. DOI: 10.19969/j.fxcsxb.22092103.
结直肠腺瘤(Colorectal adenoma,CA)发展成为结直肠癌(Colorectal cancer,CRC)是一个相对漫长而隐匿的过程,然而,目前仍缺乏微创且可靠的生物标志物来区分CA和CRC患者。该文采用超高效液相色谱-串联高分辨质谱(UHPLC-HRMS)技术结合多元统计分析方法对64例CA患者和84例CRC患者的血清样本进行代谢组学比较分析,结合,P ,<, 0.05和倍数变化 ,>, 1.50或 ,<, 0.67筛选两者的血清差异代谢物,并通过受试者工作特征曲线(ROC)分析考察其对CA和CRC的鉴别能力。同时利用差异代谢物的通路及富集分析初步探索CA癌变的代谢机制。结果表明,两组的血清代谢谱存在差异,据此筛选并鉴定获得66种组间差异代谢物,主要涉及不饱和脂肪酸的生物合成、嘌呤代谢、亚油酸代谢,提示其可能与CA癌变有关。此外,PC 36∶3、腺嘌呤、鞘氨醇、PC 18∶0、PC 20∶4标志物组合的ROC曲线下面积为0.941,对CA和CRC表现出良好的判别效能,可为CRC的临床早期预防提供有价值的参考。
Colorectal cancer(CRC) is one of the most vital causes of cancer-related death worldwide,while colorectal adenoma(CA) is an important precancerous lesion of CRC. The development of a CA into a CRC is a relatively long and stealthy process.However,there is still a lack of minimally invasive and reliable biomarkers to distinguish CA from CRC.In this paper,an ultrahigh-performance liquid chromatography-tandem high-resolution mass spectrometry(UHPLC-HRMS) combined with multivariate statistical analysis was used to analyze the untargeted metabolomics of serum samples from 64 CA patients and 84 CRC patients.The acquired metabolomics data were analyzed by unsupervised segregation principal component analysis(PCA) to visualize the grouping trends and detect outliers.A supervised orthogonal partial least squares discriminant analysis(OPLS-DA) was subsequently utilized to maximize the discrimination between the groups.The established OPLS-DA model was validated by 200 times of permutation tests to confirm its rationality and reliability in data analysis.Then the serum differential metabolites responsible for the discrimination between the groups were screened based on the criteria of ,P,<, 0.05 and fold change ,>, 1.50 or ,<, 0.67,and further identified using the mzCloud and HMDB databases.The discriminative ability for differential metabolites was verified by receiver operating characteristic(ROC) analysis.Moreover,the pathway and enrichment analyses of differential metabolites using MetaboAnalyst were used to preliminarily explore the metabolic mechanism of CA cancerization.Results showed that there were certain differences in serum metabolic profiles between the two groups,and 66 differential metabolites were screened and identified,including glycerophospholipids,fatty acids,sphingomyelins,steroids,amino acids,nucleosides and cholines.These differential metabolites mainly involved in the biosynthesis of unsaturated fatty acids,purine metabolism and linoleic acid metabolism,suggesting that they may be closely related to the carcinogenesis of CA.11 metabolic biomarkers including adenine,PC18∶0,arachidonic acid,docosahexaenoic acid,PC 36∶3,8,11,14-eicosatrienoic acid,PC 20∶4,SM d36∶2,5,8,11,14,17-eicosapentaenoic acid,sphingosine(d18∶1),and ACar 20∶1 showed good specificity and sensitivity with the area under the ROC curves greater than 0.80,which had the strong discriminant ability and high potential in clinical application to distinguish CA and CRC.Especially,the area under the ROC curve of the marker panel including PC 36∶3,adenine,sphingosine,PC 18∶0,and PC 20∶4 was 0.941,which presented an outstanding discriminant performance on the CA and CRC.The marker panel discovered provides a valuable reference for the early prevention of CRC clinically.
结直肠癌结直肠腺瘤超高效液相色谱-串联高分辨质谱(UHPLC-HRMS)血清代谢组学生物标志物
colorectal cancercolorectal adenomaultrahigh-performance liquid chromatography-tandem high-resolution mass spectrometry(UHPLC-HRMS)serum metabolomicsbiomarkers
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