Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared With Plasma miRNAs for Large-Artery Atherosclerosis Stroke

Recently, exosomal miRNAs have been reported to be associated with some diseases, and these miRNAs can be used for diagnosis and treatment. However, diagnostic biomarkers of exosomal miRNAs for ischemic stroke have rarely been studied. In the present study, we aimed to identify exosomal miRNAs that...

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Main Authors: Mengying Niu, Hong Li, Xu Li, Xiaoqian Yan, Aijun Ma, Xudong Pan, Xiaoyan Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.791644/full
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author Mengying Niu
Hong Li
Xu Li
Xiaoqian Yan
Aijun Ma
Xudong Pan
Xudong Pan
Xiaoyan Zhu
author_facet Mengying Niu
Hong Li
Xu Li
Xiaoqian Yan
Aijun Ma
Xudong Pan
Xudong Pan
Xiaoyan Zhu
author_sort Mengying Niu
collection DOAJ
description Recently, exosomal miRNAs have been reported to be associated with some diseases, and these miRNAs can be used for diagnosis and treatment. However, diagnostic biomarkers of exosomal miRNAs for ischemic stroke have rarely been studied. In the present study, we aimed to identify exosomal miRNAs that are associated with large-artery atherosclerosis (LAA) stroke, the most common subtype of ischemic stroke; to further verify their diagnostic efficiency; and to obtain promising biomarkers. High-throughput sequencing was performed on samples from 10 subjects. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on exosomes and plasma in the discovery phase (66 subjects in total) and the validation phase (520 subjects in total). We identified 5 candidate differentially expressed miRNAs (miR-369-3p, miR-493-3p, miR-379-5p, miR-1296-5p, and miR-1277-5p) in the discovery phase according to their biological functions, 4 of which (miR-369-3p, miR-493-3p, miR-379-5p, and miR-1296-5p) were confirmed in the validation phase. These four exosomal miRNAs could be used to distinguish LAA samples from small artery occlusion (SAO) samples, LAA samples from atherosclerosis (AS) samples, and LAA samples from control samples and were superior to plasma miRNAs. In addition, composite biomarkers achieved higher area under the curve (AUC) values than single biomarkers. According to our analysis, the expression levels of exosomal miR-493-3p and miR-1296-5p were negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score. The four identified exosomal miRNAs are promising biomarkers for the diagnosis of LAA stroke, and their diagnostic efficiency is superior to that of their counterparts in plasma.
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spelling doaj.art-94ec35cfb8a34d76b03a8c77a2914cc32022-12-21T18:31:51ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-11-011210.3389/fphar.2021.791644791644Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared With Plasma miRNAs for Large-Artery Atherosclerosis StrokeMengying Niu0Hong Li1Xu Li2Xiaoqian Yan3Aijun Ma4Xudong Pan5Xudong Pan6Xiaoyan Zhu7Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaInstitute of Cerebrovascular Diseases, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaInstitute of Cerebrovascular Diseases, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, ChinaRecently, exosomal miRNAs have been reported to be associated with some diseases, and these miRNAs can be used for diagnosis and treatment. However, diagnostic biomarkers of exosomal miRNAs for ischemic stroke have rarely been studied. In the present study, we aimed to identify exosomal miRNAs that are associated with large-artery atherosclerosis (LAA) stroke, the most common subtype of ischemic stroke; to further verify their diagnostic efficiency; and to obtain promising biomarkers. High-throughput sequencing was performed on samples from 10 subjects. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on exosomes and plasma in the discovery phase (66 subjects in total) and the validation phase (520 subjects in total). We identified 5 candidate differentially expressed miRNAs (miR-369-3p, miR-493-3p, miR-379-5p, miR-1296-5p, and miR-1277-5p) in the discovery phase according to their biological functions, 4 of which (miR-369-3p, miR-493-3p, miR-379-5p, and miR-1296-5p) were confirmed in the validation phase. These four exosomal miRNAs could be used to distinguish LAA samples from small artery occlusion (SAO) samples, LAA samples from atherosclerosis (AS) samples, and LAA samples from control samples and were superior to plasma miRNAs. In addition, composite biomarkers achieved higher area under the curve (AUC) values than single biomarkers. According to our analysis, the expression levels of exosomal miR-493-3p and miR-1296-5p were negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score. The four identified exosomal miRNAs are promising biomarkers for the diagnosis of LAA stroke, and their diagnostic efficiency is superior to that of their counterparts in plasma.https://www.frontiersin.org/articles/10.3389/fphar.2021.791644/fullischemic strokebiomarkersexosomesmiRNAatherosclerosis
spellingShingle Mengying Niu
Hong Li
Xu Li
Xiaoqian Yan
Aijun Ma
Xudong Pan
Xudong Pan
Xiaoyan Zhu
Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared With Plasma miRNAs for Large-Artery Atherosclerosis Stroke
Frontiers in Pharmacology
ischemic stroke
biomarkers
exosomes
miRNA
atherosclerosis
title Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared With Plasma miRNAs for Large-Artery Atherosclerosis Stroke
title_full Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared With Plasma miRNAs for Large-Artery Atherosclerosis Stroke
title_fullStr Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared With Plasma miRNAs for Large-Artery Atherosclerosis Stroke
title_full_unstemmed Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared With Plasma miRNAs for Large-Artery Atherosclerosis Stroke
title_short Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared With Plasma miRNAs for Large-Artery Atherosclerosis Stroke
title_sort circulating exosomal mirnas as novel biomarkers perform superior diagnostic efficiency compared with plasma mirnas for large artery atherosclerosis stroke
topic ischemic stroke
biomarkers
exosomes
miRNA
atherosclerosis
url https://www.frontiersin.org/articles/10.3389/fphar.2021.791644/full
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