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  

Exploration on Biomarkers for Discrimination of Colorectal Adenoma and Cancer by UHPLC-HRMS-based Serum Metabolomics

作　　者：杨珊伊 陈鸿炜 周海琳 朱一帆 张嘉豪 王旋成 黄宗声 张淇淞 YANG Shan-yi;CHEN Hong-wei;ZHOU Hai-lin;ZHU Yi-fan;ZHANG Jia-hao;WANG Xuan-cheng;HUANG Zong-sheng;ZHANG Qi-song(Medical College,Guangxi University,Nanning 530004,China;Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases,Hubei Minzu University,Enshi 445000,China;Department of Gastroenterology,The People's Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,China)

机构地区：[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

出　　处：《分析测试学报》2023年第2期173-180,共8页Journal of Instrumental Analysis

基　　金：广西大学高层次人才基金项目(A3370051006);广西巴马县科技人才专项(AE33700024);广西研究生教育创新计划资助项目(YCSW2022076);湖北民族大学风湿性疾病发生与干预湖北省重点实验室基金项目(PT0222203)。

摘　　要：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

关 键 词：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 

分 类 号：O657.63[理学—分析化学] O657.7[理学—化学]