APOE as potential biomarkers of moyamoya disease

Haibin Wu; Jiang Xu; Jiarong Sun; Jian Duan; Jinlin Xiao; Quan Ren; Pengfei Zhou; Jian Yan; Youping Li; Xiaoxing Xiong; Erming Zeng

doi:10.3389/fneur.2023.1156894

APOE as potential biomarkers of moyamoya disease

Front Neurol. 2023 May 9:14:1156894. doi: 10.3389/fneur.2023.1156894. eCollection 2023.

Authors

Haibin Wu^#¹, Jiang Xu^#¹, Jiarong Sun^#¹, Jian Duan¹, Jinlin Xiao¹, Quan Ren¹, Pengfei Zhou¹, Jian Yan¹, Youping Li¹, Xiaoxing Xiong², Erming Zeng¹

Affiliations

¹ Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
² Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.

^# Contributed equally.

Abstract

Objective: The 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.

Methods: Serum 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.

Results: We 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.

Conclusions: We 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.

Keywords: apolipoprotein E; biomarkers; carotid artery; cholesterol; moyamoya disease.

Grants and funding

This work was supported financially by the Natural Science Foundation of Jiangxi Province (Grant 20192BAB205046), the Natural Science Foundation of Jiangxi Province (Grant 20202BABL216049), the National Key R&D Program of Jiangxi Province (Grant 20202BBG73030), and the Science and Technology Key Project of Jiangxi Provincial Education Department (Grant GJJ190005).