Novel biomarkers identifying hypertrophic cardiomyopathy and its obstructive variant based on targeted amino acid metabolomics

作     者：Lanyan Guo Bo Wang Fuyang Zhang Chao Gao Guangyu Hu Mengyao Zhou Rutao Wang Hang Zhao Wenjun Yan Ling Zhang Zhiling Ma Weiping Yang Xiong Guo Chong Huang Zhe Cui Fangfang Sun Dandan Song Liwen Liu Ling Tao Lanyan Guo;Bo Wang;Fuyang Zhang;Chao Gao;Guangyu Hu;Mengyao Zhou;Rutao Wang;Hang Zhao;Wenjun Yan;Ling Zhang;Zhiling Ma;Weiping Yang;Xiong Guo;Chong Huang;Zhe Cui;Fangfang Sun;Dandan Song;Liwen Liu;Ling Tao

作者机构：Department of CardiologyXjing HospitalThe Fourth Military Medical UniversityXi'anShaanxi 710032China Department of UltrasoundXijing HospitalThe Fourth Military Medical UniversityXi'anShaanxi 710032China. 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2022年第135卷第16期

页      面：1952-1961页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：funded by the National Key Research&Development Program of China(No.2018YFA0107400) Program for Chang-Jiang Scholars and Innovative Research Team in University(No.PCSIRT-14R08) 

主　　题：Hypertrophic cardiomyopathy Amino acids Targeted metabolomics Biomarkers Algorithm 

摘      要：Background:Hypertrophic cardiomyopathy(HCM)is an underdiagnosed genetic heart disease *** management and prognosis of obstructive HCM(HOCM)and non-obstructive HCM(HNCM)are quite different,but it also remains challenging to discriminate these two *** is characterized by dysmetabolism,and myocardial amino acid(AA)metabolism is robustly *** present study aimed to delineate plasma AA and derivatives profiles,and identify potential biomarkers for ***:Plasma samples from 166 participants,including 57 cases of HOCM,52 cases of HNCM,and 57 normal controls(NCs),who first visited the International Cooperation Center for HCM,Xijing Hospital between December 2019 and September 2020,were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA *** separate classification algorithms,including random forest,support vector machine,and logistic regression,were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from ***:The univariate analysis showed that the serine,glycine,proline,citrulline,glutamine,cystine,creatinine,cysteine,choline,and aminoadipic acid levels in the HCM group were significantly different from those in the NC *** AAs and derivatives(Panel A;proline,glycine,cysteine,and choline)were screened out by multiple feature selection algorithms for discriminating HCM patients from *** receiver operating characteristic(ROC)analysis in Panel A yielded an area under the ROC curve(AUC)of 0.83(0.75-0.91)in the training set and 0.79(0.65-0.94)in the validation ***,among 10 AAs and derivatives(arginine,phenylalanine,tyrosine,proline,alanine,asparagine,creatine,tryptophan,ornithine,and choline)with statistical significance between HOCM and HNCM,3 AAs(Panel B;arginine,proline,and ornithine)were selected to differentiate the two *** A