Abstract
Clinically-informative biomarkers of ischemic stroke are needed for rapid diagnosis and timely treatment. In the present study, APOA1 unique peptide (APOA1-UP), a novel peptide biomarker, was identified and quantified by multiple reaction monitoring (MRM) using labeled reference peptide (LRP). Serum samples of 94 patients in the ischemic stroke group and 37 patients in the non-stroke group were analyzed for the levels of total APOA1-UP, low density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC). Median ratio of total APOA1-UP/LRP was 2.14 (interquartile range, 0.40) in the non-stroke group and 1.32 (0.44) in the ischemic stroke group (p < 0.0001). The serum level of total APOA1-UP was independently correlated with the presence of ischemic stroke by multivariate logistic regression analysis (p < 0.0001). From the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9750 and the optimal cutoff value of the serum APOA1-UP level was 1.80, which yielded a sensitivity of 90.63% and a specificity of 97.14%. The diagnostic efficiency of HDL-C was lower, with an AUC of 0.7488. Therefore, the serum level of APOA1-UP is a diagnostic biomarker candidate for ischemic stroke in the early stage.
Highlights
Apolipoprotein A1 (APOA1) is the major protein component of high-density lipoprotein (HDL) complexes and plays an important role in the transportation of cholesterol from peripheral tissues to the liver for excretion or reutilization
In several cross-sectional studies, higher serum levels of APOA1 and high-density lipoprotein cholesterol (HDL-C) were found in healthy subjects and considered as protective factors, whereas lower levels of APOA1 and HDL-C were associated with higher risks of the acute onset of ischemic stroke [1,2]
Ninety four patients with acute ischemic stroke were enrolled in this study as the stroke group and 37 patients with peripheral neuropathy, glioblastoma, ependymoma, or meningioma were included as the control group or non-stroke group
Summary
Apolipoprotein A1 (APOA1) is the major protein component of high-density lipoprotein (HDL) complexes and plays an important role in the transportation of cholesterol from peripheral tissues to the liver for excretion or reutilization. Proteins are broken down into fragments before they are excreted or recycled [11] Both integrate and fragmental proteins can be digested into peptides and those peptides, with unique sequences, can be detected and quantified by multiple reaction monitoring (MRM) using triple-quadrupole mass spectrometry. In 2015, Lian et al [12] developed a labeled reference peptide (LRP) method that used a single labeled peptide as a reference standard for all targeted peptides and measured peptides based on their peak areas for detected MRM transitions. Unique peptides from all possible variants of APOA1 protein in the serum can be identified and quantified by MRM-LRP as a potential clinical laboratory test
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