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Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia

BACKGROUND: The pathophysiological mechanisms of intermittent claudication (IC) progression to chronic limb-threatening ischemia (CLTI) are still vague and which of patients with IC will become CLTI are unknown. This study aimed to investigate the key molecules and pathways mediating IC progression...

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Autores principales: Yao, Ziping, Zhang, Bihui, Niu, Guochen, Yan, Ziguang, Tong, Xiaoqiang, Zou, Yinghua, Yang, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010542/
https://www.ncbi.nlm.nih.gov/pubmed/35433866
http://dx.doi.org/10.3389/fcvm.2022.864461
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author Yao, Ziping
Zhang, Bihui
Niu, Guochen
Yan, Ziguang
Tong, Xiaoqiang
Zou, Yinghua
Yang, Min
author_facet Yao, Ziping
Zhang, Bihui
Niu, Guochen
Yan, Ziguang
Tong, Xiaoqiang
Zou, Yinghua
Yang, Min
author_sort Yao, Ziping
collection PubMed
description BACKGROUND: The pathophysiological mechanisms of intermittent claudication (IC) progression to chronic limb-threatening ischemia (CLTI) are still vague and which of patients with IC will become CLTI are unknown. This study aimed to investigate the key molecules and pathways mediating IC progression to CLTI by a quantitative bioinformatic analysis of a public RNA-sequencing database of patients with peripheral artery disease (PAD) to screen biomarkers discriminating IC and CLTI. METHODS: The GSE120642 dataset was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between IC and CLTI tissues were analyzed using the “edgeR” packages of R. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the functions of DEGs. Protein–protein interaction (PPI) networks were established by the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape software. Hub genes were selected by plugin cytoHubba. Gene set enrichment analysis was performed and the receiver operating characteristic curves were used to evaluate the predictive values of hub genes. RESULTS: A total of 137 upregulated and 21 downregulated DEGs were identified. Functional enrichment clustering analysis revealed a significant association between DEGs and the complement and coagulation cascade pathways. The PPI network was constructed with 155 nodes and 105 interactions. The most significantly enriched pathway was complement activation. C1QB, C1QA, C1QC, C4A, and C1R were identified and validated as hub genes due to the high degree of connectivity. The area under the curve values for the five hub genes were greater than 0.95, indicating high accuracy for discriminating IC and CLTI. CONCLUSION: The complement activation pathway is associated with IC progression to CLTI. C1QB, C1QA, C1QC, C4A, and C1R might serve as potential early biomarkers of CLTI.
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spelling pubmed-90105422022-04-16 Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia Yao, Ziping Zhang, Bihui Niu, Guochen Yan, Ziguang Tong, Xiaoqiang Zou, Yinghua Yang, Min Front Cardiovasc Med Cardiovascular Medicine BACKGROUND: The pathophysiological mechanisms of intermittent claudication (IC) progression to chronic limb-threatening ischemia (CLTI) are still vague and which of patients with IC will become CLTI are unknown. This study aimed to investigate the key molecules and pathways mediating IC progression to CLTI by a quantitative bioinformatic analysis of a public RNA-sequencing database of patients with peripheral artery disease (PAD) to screen biomarkers discriminating IC and CLTI. METHODS: The GSE120642 dataset was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between IC and CLTI tissues were analyzed using the “edgeR” packages of R. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the functions of DEGs. Protein–protein interaction (PPI) networks were established by the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape software. Hub genes were selected by plugin cytoHubba. Gene set enrichment analysis was performed and the receiver operating characteristic curves were used to evaluate the predictive values of hub genes. RESULTS: A total of 137 upregulated and 21 downregulated DEGs were identified. Functional enrichment clustering analysis revealed a significant association between DEGs and the complement and coagulation cascade pathways. The PPI network was constructed with 155 nodes and 105 interactions. The most significantly enriched pathway was complement activation. C1QB, C1QA, C1QC, C4A, and C1R were identified and validated as hub genes due to the high degree of connectivity. The area under the curve values for the five hub genes were greater than 0.95, indicating high accuracy for discriminating IC and CLTI. CONCLUSION: The complement activation pathway is associated with IC progression to CLTI. C1QB, C1QA, C1QC, C4A, and C1R might serve as potential early biomarkers of CLTI. Frontiers Media S.A. 2022-04-01 /pmc/articles/PMC9010542/ /pubmed/35433866 http://dx.doi.org/10.3389/fcvm.2022.864461 Text en Copyright © 2022 Yao, Zhang, Niu, Yan, Tong, Zou and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Yao, Ziping
Zhang, Bihui
Niu, Guochen
Yan, Ziguang
Tong, Xiaoqiang
Zou, Yinghua
Yang, Min
Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia
title Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia
title_full Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia
title_fullStr Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia
title_full_unstemmed Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia
title_short Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia
title_sort subunits of c1q are associated with the progression of intermittent claudication to chronic limb-threatening ischemia
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010542/
https://www.ncbi.nlm.nih.gov/pubmed/35433866
http://dx.doi.org/10.3389/fcvm.2022.864461
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