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pmid:36035208

Novel Diagnostic Biomarkers Related to Oxidative Stress and Macrophage Ferroptosis in Atherosclerosis.

Minhui Li · Siyuan Xin · Ruiyuan Gu · Lin Zheng · Jie Hu · Ruijing Zhang · Honglin Dong

Oxidative medicine and cellular longevity · 2022 doi:10.1155/2022/8917947

Paper

complete

Experiment

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Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:36035208
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science-record
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2026-11-01T18:15:12Z
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2026-11-01T22:49:55Z
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paper object · 10 fields
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complete
title
Novel Diagnostic Biomarkers Related to Oxidative Stress and Macrophage Ferroptosis in Atherosclerosis.
doi
10.1155/2022/8917947
pmid
36035208
authors array · 7 items
[0]
Minhui Li
[1]
Siyuan Xin
[2]
Ruiyuan Gu
[3]
Lin Zheng
[4]
Jie Hu
[5]
Ruijing Zhang
[6]
Honglin Dong
journal
Oxidative medicine and cellular longevity
year
2022
abstract
Atherosclerosis (AS) is a chronic inflammatory disease, which has a complex interplay between altered immune metabolism and oxidative stress. Therefore, we aimed to determine the oxidative stress and immune-related biomarkers in AS. Differential gene expression analyses are based on the GSE100927 dataset in the Gene Expression Omnibus (GEO), and 389 oxidative stress (OS) genes are identified based on gene set enrichment analysis (GSEA). We identified 74 differentially expressed genes related to oxidative stress (DEOSGs). "CIBERSORT" and "WGCNA" R Packages were used to compare the differences in immune infiltration levels between AS and control samples. The DEOSGs (N = 74) were intersected with the key module's genes of WGCNA (N = 972), and 27 differentially expressed immune-related oxidative stress genes (DEIOSGs) were obtained. To identify the pivotal genes, a protein-protein interaction (PPI) network was constructed using the STRING database and the Cytoscape software. MMP9, ALOX5, NCF2, NCF, and NCF4 were identified as diagnostic markers of AS, and we validated them in the GSE57691 dataset. The expression levels of the five diagnostic genes were significantly highly expressed in the AS group. Correlation analysis and single-cell analysis revealed that five diagnostic genes were mainly correlated with macrophages M1. We, respectively, intersected differentially expressed genes (DEGs) with ferroptosis gene set, necroptosis gene set, and pyroptosis gene set. The findings suggested that ALOX5 and NCF2 were differentially expressed genes of ferroptosis. High expression of five hub genes in RAW264.7 macrophages were confirmed by PCR. High ALOX5 and NCF2 expression levels in plaque tissues were confirmed by immunohistochemistry (IHC) and western blotting. Our study identified that MMP9, ALOX5, NCF2, NCF1, and NCF4 were diagnostic genes of AS and associated with oxidative stress. ALOX5 and NCF2 may be involved in the formation of the necrotic core in AS by regulating macrophage ferroptosis.
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The differentially expressed genes (DEGs) from GSE100927 were identified using the Limma R package on normalized count data. The parameters |Log2fold change| >0.5 and adj. P < 0.05 were used as the screening criteria for DEGs.
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sections[4] "2.2. Identification of DEGs" paragraph 2
quote
The differentially expressed genes (DEGs) from GSE100927 were identified using the Limma R package on normalized count data. The parameters |Log2fold change| >0.5 and adj. P < 0.05 were used as the screening criteria for DEGs.
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sections[31] "Data Availability" paragraph 2
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The analysis data used to support the findings of this study are available from the corresponding author upon request.
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Limma-based differential gene expression analysis of GSE100927 identified 2,417 differentially expressed genes between atherosclerotic and control samples.
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Differential gene expression analysis was performed using GSE100927. A total of 2417 DEGs (|log2FC| >0.5 and adjusted P < 0.05) were obtained, of which 934 DEGs were downregulated and 1483 were upregulated.
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sections[17] "3.1. Identification of DEGs" paragraph 2
quote
Differential gene expression analysis was performed using GSE100927. A total of 2417 DEGs (|log2FC| >0.5 and adjusted P < 0.05) were obtained, of which 934 DEGs were downregulated and 1483 were upregulated.
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Limma-based differential gene expression analysis of GSE100927 identified 2,417 differentially expressed genes between atherosclerotic and control samples.
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Atherosclerotic and control peripheral artery gene expression
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The differentially expressed genes (DEGs) from GSE100927 were identified using the Limma R package on normalized count data. The parameters |Log2fold change| >0.5 and adj. P < 0.05 were used as the screening criteria for DEGs.
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n levels in plaque tissues were confirmed by immunohistochemistry (IHC) and western blotting. Our study identi
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confirmed by immunohistochemistry (IHC) and western blotting. Our study identified that MMP9, ALOX5, NCF2
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Complete file
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Therefore, we aimed to determine the oxidative stress and immune-related biomarkers in AS. Differential gene expression analyses are based on the GSE100927 dataset in the Gene Expression Omnibus (GEO), and 389 oxidative stress (OS) genes are identified based on gene set enrichment analysis (GSEA). We identified 74 differentially expressed genes related to oxidative stress (DEOSGs). \"CIBERSORT\" and \"WGCNA\" R Packages were used to compare the differences in immune infiltration levels between AS and control samples. The DEOSGs (N = 74) were intersected with the key module's genes of WGCNA (N = 972), and 27 differentially expressed immune-related oxidative stress genes (DEIOSGs) were obtained. To identify the pivotal genes, a protein-protein interaction (PPI) network was constructed using the STRING database and the Cytoscape software. MMP9, ALOX5, NCF2, NCF, and NCF4 were identified as diagnostic markers of AS, and we validated them in the GSE57691 dataset. The expression levels of the five diagnostic genes were significantly highly expressed in the AS group. Correlation analysis and single-cell analysis revealed that five diagnostic genes were mainly correlated with macrophages M1. We, respectively, intersected differentially expressed genes (DEGs) with ferroptosis gene set, necroptosis gene set, and pyroptosis gene set. The findings suggested that ALOX5 and NCF2 were differentially expressed genes of ferroptosis. High expression of five hub genes in RAW264.7 macrophages were confirmed by PCR. High ALOX5 and NCF2 expression levels in plaque tissues were confirmed by immunohistochemistry (IHC) and western blotting. Our study identified that MMP9, ALOX5, NCF2, NCF1, and NCF4 were diagnostic genes of AS and associated with oxidative stress. 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