Salivary metabolites are promising noninvasive biomarkers of druginduced liver injury  

作　　者：Si-Miao Yu Hao-Cheng Zheng Si-Ci Wang Wen-Ya Rong Ping Li Jing Jing Ting-Ting He Jia-Hui Li Xia Ding Rui-Lin Wang 

机构地区：[1]School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China [2]School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,Guangdong Province,China [3]Department of Hepatology of Traditional Chinese Medicine,The Fifth Medical Center of PLA General Hospital,Beijing 100039,China [4]The First Clinical Medical College,Henan University of Traditional Chinese Medicine,Zhengzhou 450000,Henan Province,China

出　　处：《World Journal of Gastroenterology》2024年第18期2454-2466,共13页世界胃肠病学杂志（英文版）

基　　金：Supported by Medical Education Association Foundation of China,No.2020KTY001;National Natural Science Foundation of China,No.81673806;National Natural Science Foundation Youth Fund,No.82104702.

摘　　要：BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.

关 键 词：Drug-Induced liver injury SALIVARY Metabolomics BIOMARKER Weighted metabolite Coexpression network analysis Machine learning NONINVASIVE Diagnostic method METABOLITES 

分 类 号：R575.2[医药卫生—消化系统] R512.62[医药卫生—内科学]