APOE as potential biomarkers of moyamoya disease

ObjectiveThe mechanisms underpinning Moyamoya disease (MMD) remain unclear, and effective biomarkers remain unknown. The purpose of this study was to identify novel serum biomarkers of MMD.MethodsSerum samples were collected from 23 patients with MMD and 30 healthy controls (HCs). Serum proteins wer...

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Main Authors: Haibin Wu, Jiang Xu, Jiarong Sun, Jian Duan, Jinlin Xiao, Quan Ren, Pengfei Zhou, Jian Yan, Youping Li, Xiaoxing Xiong, Erming Zeng
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Neurology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2023.1156894/full
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author Haibin Wu
Jiang Xu
Jiarong Sun
Jian Duan
Jinlin Xiao
Quan Ren
Pengfei Zhou
Jian Yan
Youping Li
Xiaoxing Xiong
Erming Zeng
author_facet Haibin Wu
Jiang Xu
Jiarong Sun
Jian Duan
Jinlin Xiao
Quan Ren
Pengfei Zhou
Jian Yan
Youping Li
Xiaoxing Xiong
Erming Zeng
author_sort Haibin Wu
collection DOAJ
description ObjectiveThe mechanisms underpinning Moyamoya disease (MMD) remain unclear, and effective biomarkers remain unknown. The purpose of this study was to identify novel serum biomarkers of MMD.MethodsSerum samples were collected from 23 patients with MMD and 30 healthy controls (HCs). Serum proteins were identified using tandem tandem-mass-tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) in the serum samples were identified using the SwissProt database. The DEPs were assessed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Gene Ontology (GO), and protein-protein interaction (PPI) networks, and hub genes were identified and visualized using Cytoscape software. Microarray datasets GSE157628, GSE189993, and GSE100488 from the Gene Expression Omnibus (GEO) database were collected. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were identified, and miRNA targets of DEGs were predicted using the miRWalk3.0 database. Serum apolipoprotein E (APOE) levels were compared in 33 MMD patients and 28 Moyamoya syndrome (MMS) patients to investigate the potential of APOE to be as an MMD biomarker.ResultsWe identified 85 DEPs, of which 34 were up- and 51 down-regulated. Bioinformatics analysis showed that some DEPs were significantly enriched in cholesterol metabolism. A total of 1105 DEGs were identified in the GSE157628 dataset (842 up- and 263 down-regulated), whereas 1290 were identified in the GSE189993 dataset (200 up- and 1,090 down-regulated). The APOE only overlaps with the upregulated gene expression in Proteomic Profiling and in GEO databases. Functional enrichment analysis demonstrated that APOE was associated with cholesterol metabolism. Moreover, 149 miRNAs of APOE were predicted in the miRWalk3.0 database, and hsa-miR-718 was the only DE-miRNA overlap identified in MMD samples. Serum APOE levels were significantly higher in patients with MMD than in those without. The performance of APOE as an individual biomarker to diagnose MMD was remarkable.ConclusionsWe present the first description of the protein profile of patients with MMD. APOE was identified as a potential biomarker for MMD. Cholesterol metabolism was found to potentially be related to MMD, which may provide helpful diagnostic and therapeutic insights for MMD.
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spelling doaj.art-7161068fda0c4020afa10f725f0a99fb2023-05-09T05:33:01ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-05-011410.3389/fneur.2023.11568941156894APOE as potential biomarkers of moyamoya diseaseHaibin Wu0Jiang Xu1Jiarong Sun2Jian Duan3Jinlin Xiao4Quan Ren5Pengfei Zhou6Jian Yan7Youping Li8Xiaoxing Xiong9Erming Zeng10Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaObjectiveThe mechanisms underpinning Moyamoya disease (MMD) remain unclear, and effective biomarkers remain unknown. The purpose of this study was to identify novel serum biomarkers of MMD.MethodsSerum samples were collected from 23 patients with MMD and 30 healthy controls (HCs). Serum proteins were identified using tandem tandem-mass-tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) in the serum samples were identified using the SwissProt database. The DEPs were assessed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Gene Ontology (GO), and protein-protein interaction (PPI) networks, and hub genes were identified and visualized using Cytoscape software. Microarray datasets GSE157628, GSE189993, and GSE100488 from the Gene Expression Omnibus (GEO) database were collected. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were identified, and miRNA targets of DEGs were predicted using the miRWalk3.0 database. Serum apolipoprotein E (APOE) levels were compared in 33 MMD patients and 28 Moyamoya syndrome (MMS) patients to investigate the potential of APOE to be as an MMD biomarker.ResultsWe identified 85 DEPs, of which 34 were up- and 51 down-regulated. Bioinformatics analysis showed that some DEPs were significantly enriched in cholesterol metabolism. A total of 1105 DEGs were identified in the GSE157628 dataset (842 up- and 263 down-regulated), whereas 1290 were identified in the GSE189993 dataset (200 up- and 1,090 down-regulated). The APOE only overlaps with the upregulated gene expression in Proteomic Profiling and in GEO databases. Functional enrichment analysis demonstrated that APOE was associated with cholesterol metabolism. Moreover, 149 miRNAs of APOE were predicted in the miRWalk3.0 database, and hsa-miR-718 was the only DE-miRNA overlap identified in MMD samples. Serum APOE levels were significantly higher in patients with MMD than in those without. The performance of APOE as an individual biomarker to diagnose MMD was remarkable.ConclusionsWe present the first description of the protein profile of patients with MMD. APOE was identified as a potential biomarker for MMD. Cholesterol metabolism was found to potentially be related to MMD, which may provide helpful diagnostic and therapeutic insights for MMD.https://www.frontiersin.org/articles/10.3389/fneur.2023.1156894/fullmoyamoya diseaseapolipoprotein Ebiomarkerscholesterolcarotid artery
spellingShingle Haibin Wu
Jiang Xu
Jiarong Sun
Jian Duan
Jinlin Xiao
Quan Ren
Pengfei Zhou
Jian Yan
Youping Li
Xiaoxing Xiong
Erming Zeng
APOE as potential biomarkers of moyamoya disease
Frontiers in Neurology
moyamoya disease
apolipoprotein E
biomarkers
cholesterol
carotid artery
title APOE as potential biomarkers of moyamoya disease
title_full APOE as potential biomarkers of moyamoya disease
title_fullStr APOE as potential biomarkers of moyamoya disease
title_full_unstemmed APOE as potential biomarkers of moyamoya disease
title_short APOE as potential biomarkers of moyamoya disease
title_sort apoe as potential biomarkers of moyamoya disease
topic moyamoya disease
apolipoprotein E
biomarkers
cholesterol
carotid artery
url https://www.frontiersin.org/articles/10.3389/fneur.2023.1156894/full
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