家族性腺瘤性息肉病与散发性结直肠腺瘤血清代谢物特征谱的比较分析  

Comparative analysis of serum metabolite profiles in familial adenomatous polyposis and sporadic colorectal adenoma

作　　者：尹馥梅 郭家池 许俊锋 张杰 王凤玉 潘元明 盛剑秋 YIN Fumei;GUO Jiachi;XU Junfeng;ZHANG Jie;WANG Fengyu;PAN Yuanming;SHENG Jianqiu(Medical School Chinese PLA,Beijing 100853;Department of Gastroenterology,the Seventh Medical Center of Chinese PLA General Hospital;Department of Gastroenterology,the First Medical Center of Chinese PLA General Hospital;Cancer Research Center,Beijing Chest Hospital,Capital Medical University,China)

机构地区：[1]解放军医学院,北京100853 [2]中国人民解放军总医院第七医学中心消化内科 [3]中国人民解放军总医院第一医学中心消化内科医学部 [4]首都医科大学附属北京胸科医院肿瘤研究中心

出　　处：《胃肠病学和肝病学杂志》2022年第12期1371-1376,1384,共7页Chinese Journal of Gastroenterology and Hepatology

基　　金：北京市科委科技计划课题(D171100002617001)。

摘　　要：目的比较分析家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)和散发性结直肠腺瘤(colorectal adenoma,CRA)的血清代谢物特征。方法收集2017年3月至2020年12月于中国人民解放军总医院第七医学中心行结肠镜检查的FAP和CRA患者的血清样本,使用超高效液相色谱串联质谱(ultra-high performance liquid chromatography and tandem mass-spectrometry,UPLC-MS/MS)进行定性定量分析,通过主成分分析(principal component analysis,PCA)和聚类分析(cluster analysis,CA)筛选出FAP与CRA两组的差异代谢物。结果对FAP和CRA进行检测分析,共发现了238种代谢物,采用FC(≤0.5或≥2)和OPLS-DA模型的VIP值(≥1)相结合的方法筛选出85种差异代谢物,其中表达上调的有20种,表达下调的有65种。进一步通过KEGG对差异代谢物进行功能注释和富集分析,发现与CRA组相比,FAP患者氨基酸代谢谱中的甘氨酸、天冬氨酸、异亮氨酸、谷氨酸、胱氨酸、苏氨酸、天冬酰胺、亮氨酸和瓜氨酸表达显著降低。结论UPLC-MS/MS方法能有效筛选FAP与CRA的差异代谢物。FAP特异性氨基酸谱的改变,可为其发病机制的深入研究提供新的思路,同时为疾病预警模型提供新的基础。Objective To compare and analyze the serum metabolite profiles of familial adenomatous polyposis(FAP)and sporadic colorectal adenoma(CRA).Methods Serum samples from patients with FAP and CRA who underwent colonoscopy at the Seventh Medical Center of Chinese PLA General Hospital from Mar.2017 to Dec.2020 were collected and centrifuged for qualitative and quantitative analysis using ultra-high performance liquid chromatography and tandem mass-spectrometry(UPLC-MS/MS).Principal component analysis(PCA)and cluster analysis(CA)plots were used to screen out metabolites with the statistically significant differences between CRA group and FAP group.Results A total of 238 metabolites were found in the two groups,and 85 differential metabolites were identified by combining the FC(≤0.5 or≥2)and VIP value(≥1)of the OPLS-DA model,of which 20 were up-regulated and 65 were down-regulated.Further functional annotation and enrichment analysis of differential metabolites by KEGG revealed that compared with the CRA group,glycine,aspartic acid,isoleucine,glutamic acid,cystine,threonine,asparagine,leucine,and citrulline expression were significantly reduced in FAP group.Conclusion UPLC-MS/MS method can effectively screen the differential metabolites between the FAP and CRA.The specific amino acid profile of the FAP can provide novel ideas for the in-depth study of its pathogenesis,and provide a new basis for the establishment of an early warning indicator model for disease development.

关 键 词：家族性腺瘤性息肉病 结直肠腺瘤 UPLC-MS/MS 代谢组学 氨基酸谱 

分 类 号：R735.3[医药卫生—肿瘤]