结直肠进展期腺瘤的尿液代谢组学特点初探

A preliminary study on urine metabolomics in colorectal advanced adenomas

目的分析结直肠进展期腺瘤(advanced adenoma,AA)的尿液代谢组学特点。方法纳入2020年7月至2021年12月于首都医科大学附属北京世纪坛医院消化内科住院行结直肠息肉内镜下治疗者,或伺机筛查行结肠镜检查者,收集患者的临床和内镜资料。按结肠镜和病理结果分为AA和对照组(结肠镜未见明显异常),每组30例。所有研究对象于结肠镜检查或治疗前留取晨起中段尿3~5 mL,以气相色谱-飞行时间质谱联用技术进行代谢组学检测和分析。差异代谢物的筛选基于t检验的P值<0.05和正交偏最小二乘法-判别分析(orthogonal projections to latent structures discriminant analysis,OPLS-DA)模型第一主成分的变量投影重要度(variable importance in the projection,VIP)>1。差异代谢物参考京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)旁路数据库进行KEGG分类。结果本研究包括男36例和女24例,年龄(55.9±10.8)岁(27~75岁)。AA组年龄较对照组大[(59.8±9.6)岁vs(52.0±10.7)岁,P=0.004];两组在性别构成、伴高血压、糖尿病、吸烟、恶性肿瘤家族史方面差异无统计学意义。OPLS-DA显示,AA组和对照组样本间横向距离远,出现了明显的分离趋势。共检测出37种差异代谢物;AA组尿嘧啶、3-氨基异丁酸呈显著上调,葡萄糖酸内酯、α-酮基戊二酸、酒石酸、4-羟基苯甲酸、乳果糖、苯乙酸、1,5-酐-D-山梨糖醇、3-羟基丙酮酸呈显著下调。根据KEGG通路注释的结果,将差异代谢物进行富集分析,结果显示AA组与对照组的差异代谢物涉及到氨基酸代谢、碳水化合物代谢、核苷酸代谢等,其中氨基酸代谢涉及到了苯基丙氨酸、缬氨酸、亮氨酸、异亮氨酸、半胱氨酸、蛋氨酸、甘氨酸等多条代谢通路。结论AA尿液代谢组学检测出了葡萄糖酸内酯、尿嘧啶、3-氨基异丁酸等多个差异代谢物质,涉及到氨基酸代谢、碳水化合物代谢、核苷酸代谢等。尿液质谱代谢组学有成为AA无创筛查工具的潜能。

Objective To analyze the characteristics of urine metabolomics in colorectal advanced adenoma(AA).Methods Patients who underwent endoscopic treatment of colorectal polyps or underwent colonoscopy for screening were enrolled in the Department of Gastroenterology,Beijing Shijitan Hospital,Capital Medical University from Jul.2020 to Dec.2021.And clinical and endoscopic data were collected.According to colonoscopy and pathological results,the patients were divided into AA and control group(no obvious abnormality was observed by colonoscopy),with 30 cases in each group.Mid-morning urine(3-5 mL)was collected from all subjects before colonoscopy or treatment,and metabolomics was detected and analyzed by gas chromatography-time-of-flight mass spectrometry.Differential metabolites screening was based on Student′s t-test with P values less than 0.05 and orthogonal projections to latent structures discriminant analysis(OPLS-DA).The variable importance in the projection(VIP)of the first principal component of OPLS-DA model was greater than 1.Results This study included 36 males and 24 females,with(55.9±10.8)years old,ranging from 27 to 75 years old,AA group was higher than that of control group[(59.8±9.6)years old vs(52.0±10.7)years old,P=0.004].There were no significant differences in gender composition,hypertension,diabetes,smoking and family history of malignant tumor between the two groups.OPLS-DA showed that the transverse distance between the samples of AA group and the control group was far,showing an obvious separation trend.A total of 37 different metabolites were detected.In AA group,uric acid and 3-aminoisobutyric acid were significantly up-regulated,while gluconic lactone,α-ketoglutaric acid,tartaric acid,4-hydroxybenzoic acid,lactulose,phenylacetic acid,1,5-anhydride-D-sorbitol and 3-hydroxypyruvate were significantly down-regulated.Conclusion Urine metabolomics of AA detected different metabolites such as gluconic lactone,uric acid and 3-aminoisobutyric acid.The urine mass spectrometry-based metabolomics has the potential to be a non-invasive screening method for AA.