title: Lipidomic analysis of plasma in patients with lacunar infarction using normal-phase/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry.
abstract: Stroke is a major cause of mortality and long-term disability worldwide. The study of biomarkers and pathogenesis is vital for early diagnosis and treatment of stroke. In the present study, a continuous-flow normal-phase/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (NP/RP 2D LC-QToF/MS) method was employed to measure lipid species in human plasma, including healthy controls and lacunar infarction (LI) patients. As a result, 13 lipid species were demonstrated with significant difference between the two groups, and a "plasma biomarker model" including glucosylceramide (38:2), phosphatidylethanolamine (35:2), free fatty acid (16:1), and triacylglycerol (56:5) was finally established. This model was evaluated as an effective tool in that area under the receiver operating characteristic curve reached 1.000 in the discovery set and 0.947 in the validation set for diagnosing LI patients from healthy controls. Besides, the sensitivity and specificity of disease diagnosis in validation set were 93.3% and 96.6% at the best cutoff value, respectively. This study demonstrates the promising potential of NP/RP 2D LC-QToF/MS-based lipidomics approach in finding bio-markers for disease diagnosis and providing special insights into the metabolism of stroke induced by small vessel disease. Graphical abstract Flow-chart of the plasma biomarker model establishment through biomarker screening and validation.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Pathogenesis of Cerebral Small Vessel Disease and Department of Neurology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Lv
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Wanpeng
authors.initials: W
authors.lastname: Ai
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Linnan
authors.initials: L
authors.lastname: Li
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Sensen
authors.initials: S
authors.lastname: Shen
authors.affiliation: Analytical Instrumentation Center, Peking University, Beijing, 100871, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Nie
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.|National Research Center for Geoanalysis, Beijing, 100037, China.
authors.forename: Yabing
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Beijing Key Laboratory of Pathogenesis of Cerebral Small Vessel Disease and Department of Neurology, Peking University First Hospital, Beijing, 100034, China. ynhuang@sina.com.
authors.forename: Yining
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China. hwliu@pku.edu.cn.
authors.forename: Huwei
authors.initials: H
authors.lastname: Liu
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged; D059409:Stroke, Lacunar / Q000097:blood* / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D008055:Lipids
keywords: Biomarker; Lacunar infarction; Lipidomics; NP/RP 2D LC-QToF/MS; Stroke