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Lipidomic analysis of plasma in patients with lacunar infarction using normal-phase/reversed-phase two-dimensional liquid chromatography–quadrupole time-of-flight mass spectrometry

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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.

Flow-chart of the plasma biomarker model establishment through biomarker screening and validation

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Abbreviations

ARIC:

Atherosclerosis risk in communities

AUC:

Area under the curve

BPCs:

Base peak chromatograms

CEF:

Compound exchange format

Cer:

Ceramide

DG:

Diacylglycerol

EICs:

Extracted ion chromatograms

ESM:

Electronic supplementary material

FDR:

False discovery rate

FFA:

Free fatty acids

GalCer:

Galactosylceramide

GCS:

Glucosylceramide synthase

GluCer:

Glucosylceramide

LacCer:

Lactosylceramide

LI:

Lacunar infarction

LPC:

Lysophosphatidylcholine

LPE:

Lysophosphatidylethanolamine

LPG:

Lysophosphatidylglycerol

MG:

Monoacylglycerol

MPP:

Mass profiler professional

MS/MS:

Tandem mass spectra

NP/RP 2D LC-QToF/MS:

Normal-phase/reversed-phase two-dimensional liquid chromatography–quadrupole time-of-flight mass spectrometry

PC:

Phosphatidylcholine

PCA:

Principal component analysis

PE:

Phosphatidylethanolamine

PG:

Phosphatidylglycerol

PI:

Phosphatidylinositol

PLA2 :

Phospholipase A2

PS:

Phosphatidylserine

ROC:

Receiver operating characteristic

SM:

Sphingomyelin

TG:

Triacylglycerol

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Acknowledgements

This study was financially supported by the National Natural Science Foundation of China (grant numbers, 21527809 and 21175005).

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Author notes

    Authors and Affiliations

    1. 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

      Li Yang, Wanpeng Ai, Linnan Li, Sensen Shen, Yabing Shan, Yu Bai & Huwei Liu

    2. Beijing Key Laboratory of Pathogenesis of Cerebral Small Vessel Disease and Department of Neurology, Peking University First Hospital, Beijing, 100034, China

      Pu Lv & Yining Huang

    3. Analytical Instrumentation Center, Peking University, Beijing, 100871, China

      Honggang Nie

    4. National Research Center for Geoanalysis, Beijing, 100037, China

      Yabing Shan

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    1. Li Yang
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    Correspondence to Yining Huang or Huwei Liu.

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    The authors declare that they have no conflict of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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    Informed consent was obtained from all individual participants included in the study.

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    Li Yang and Pu Lv contributed equally to this work.

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    Yang, L., Lv, P., Ai, W. et al. Lipidomic analysis of plasma in patients with lacunar infarction using normal-phase/reversed-phase two-dimensional liquid chromatography–quadrupole time-of-flight mass spectrometry. Anal Bioanal Chem 409, 3211–3222 (2017). https://doi.org/10.1007/s00216-017-0261-6

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