title: Discovery of Metabolite Biomarkers for Acute Ischemic Stroke Progression.
abstract: Stroke remains a major public health problem worldwide; it causes severe disability and is associated with high mortality rates. However, early diagnosis of stroke is difficult, and no reliable biomarkers are currently established. In this study, mass-spectrometry-based metabolomics was utilized to characterize the metabolic features of the serum of patients with acute ischemic stroke (AIS) to identify novel sensitive biomarkers for diagnosis and progression. First, global metabolic profiling was performed on a training set of 80 human serum samples (40 cases and 40 controls). The metabolic profiling identified significant alterations in a series of 26 metabolites with related metabolic pathways involving amino acid, fatty acid, phospholipid, and choline metabolism. Subsequently, multiple algorithms were run on a test set consisting of 49 serum samples (26 cases and 23 controls) to develop different classifiers for verifying and evaluating potential biomarkers. Finally, a panel of five differential metabolites, including serine, isoleucine, betaine, PC(5:0/5:0), and LysoPE(18:2), exhibited potential to differentiate AIS samples from healthy control samples, with area under the receiver operating characteristic curve values of 0.988 and 0.971 in the training and test sets, respectively. These findings provided insights for the development of new diagnostic tests and therapeutic approaches for AIS.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University , Xuefu Road No. 246, Harbin 150001, China.|Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education , Xuefu Road No. 246, Harbin 150001, China.
authors.forename: Peifang
authors.initials: P
authors.lastname: Liu
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education , Tongjia Lane No. 24, Nanjing 210009, China.
authors.forename: Ruiting
authors.initials: R
authors.lastname: Li
authors.affiliation: Accendo Data LLC , Coral Springs, Florida 33067, United States.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Antonov
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University , Xuefu Road No. 246, Harbin 150001, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education , Tongjia Lane No. 24, Nanjing 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education , Tongjia Lane No. 24, Nanjing 210009, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education , Tongjia Lane No. 24, Nanjing 210009, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Guo
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education , Tongjia Lane No. 24, Nanjing 210009, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University , Xuefu Road No. 246, Harbin 150001, China.
authors.forename: Peijia
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University , Xuefu Road No. 246, Harbin 150001, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education , Tongjia Lane No. 24, Nanjing 210009, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education , Tongjia Lane No. 24, Nanjing 210009, China.
authors.forename: Fengguo
authors.initials: F
authors.lastname: Xu
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education , Tongjia Lane No. 24, Nanjing 210009, China.
authors.forename: Zunjian
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University , Xuefu Road No. 246, Harbin 150001, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education , Xuefu Road No. 246, Harbin 150001, China.|Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education , Tongjia Lane No. 24, Nanjing 210009, China.
authors.forename: Yin
authors.identifier: 0000-0001-9678-2630
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000368:Aged; D001622:Betaine / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007532:Isoleucine / Q000097:blood; D008297:Male; D055442:Metabolome / Q000235:genetics*; D055432:Metabolomics; D008875:Middle Aged; D012372:ROC Curve; D012694:Serine / Q000097:blood; D020521:Stroke / Q000097:blood* / Q000473:pathology
chemical_list: D015415:Biomarkers; D007532:Isoleucine; D001622:Betaine; D012694:Serine
keywords: acute ischemic stroke; classify; human serum biomarkers; logistic regression; mass spectrometry; metabolomics