Identification of key genes and regulatory networks involved in the Comorbidity of atrial fibrillation and chronic obstructive pulmonary disease

Background: The underlying molecular processes of atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) are frequently linked to increased morbidity and mortality when they co-occur. However, their underlying molecular mechanisms are questioned due to their incomplete analysis. O...

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Main Authors: Shan Xiong, Qiming Liu, Shenghua Zhou, Yichao Xiao
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S240584402309638X
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author Shan Xiong
Qiming Liu
Shenghua Zhou
Yichao Xiao
author_facet Shan Xiong
Qiming Liu
Shenghua Zhou
Yichao Xiao
author_sort Shan Xiong
collection DOAJ
description Background: The underlying molecular processes of atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) are frequently linked to increased morbidity and mortality when they co-occur. However, their underlying molecular mechanisms are questioned due to their incomplete analysis. Objective: This study aimed to identify common differentially expressed genes (DEGs) in AF and COPD patients and investigate their potential biological functions and pathways. We hope to complement and update previous research through clearer figure presentation and different bioinformatic analysis methods with different datasets. Methods: We used statistical analysis to identify DEGs in the expression profiles of AF and COPD patients using datasets from the Gene Expression Omnibus database. To ascertain whether the common DEGs were functionally enriched, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used. In addition, we generated protein‒protein interaction networks and identified significant hub genes. Furthermore, the hub genes were used to analyze transcription factor (TF)-gene interactions and TF-miRNA coregulatory networks, and their expression levels were validated in additional datasets. Results: We identified a total of 15 DEGs that were upregulated, whereas 36 were downregulated in AF and COPD patients. The DEGs were commonly expressed in both AF and COPD patients, with functional enrichment analysis revealing their involvement in metabolic processes and neuron-to-neuron synapses. We identified significant hub genes, including TGM2, ITPR1, CHL1, ALDOC, RPS3, FBLN2, NDUFS2, ITGA5, CTNNB1, RBP1, CLSTN2, FABP5, EPHA4, LDHA, and HNRNPL, and analyzed their coexpression and biological functions. TF-gene interaction and TF-miRNA coregulatory network analyses revealed the regulatory relationships of the hub genes. Additional datasets were analyzed to validate hub gene expression, and ALDOC, HNRNPL, and NDUFS2 displayed similar processes in AF and COPD patients. Conclusions: In our study, we demonstrate that metabolic processes and neuron-to-neuron synaptic connections may contribute to the cooccurrence of AF and COPD. The identified hub genes and regulatory networks may act as potential biomarkers and therapeutic targets for these diseases.
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spelling doaj.art-83778b3cdf3f4df09e1655949d13285b2023-12-02T07:05:57ZengElsevierHeliyon2405-84402023-11-01911e22430Identification of key genes and regulatory networks involved in the Comorbidity of atrial fibrillation and chronic obstructive pulmonary diseaseShan Xiong0Qiming Liu1Shenghua Zhou2Yichao Xiao3Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, China; Xiangya School of Medicine, Central South University, Changsha, ChinaDepartment of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, China; Corresponding author. Department of Cardiovascular Medicine, Second Xiangya Hospital of Central South University, Changsha, Hunan, China.Background: The underlying molecular processes of atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) are frequently linked to increased morbidity and mortality when they co-occur. However, their underlying molecular mechanisms are questioned due to their incomplete analysis. Objective: This study aimed to identify common differentially expressed genes (DEGs) in AF and COPD patients and investigate their potential biological functions and pathways. We hope to complement and update previous research through clearer figure presentation and different bioinformatic analysis methods with different datasets. Methods: We used statistical analysis to identify DEGs in the expression profiles of AF and COPD patients using datasets from the Gene Expression Omnibus database. To ascertain whether the common DEGs were functionally enriched, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used. In addition, we generated protein‒protein interaction networks and identified significant hub genes. Furthermore, the hub genes were used to analyze transcription factor (TF)-gene interactions and TF-miRNA coregulatory networks, and their expression levels were validated in additional datasets. Results: We identified a total of 15 DEGs that were upregulated, whereas 36 were downregulated in AF and COPD patients. The DEGs were commonly expressed in both AF and COPD patients, with functional enrichment analysis revealing their involvement in metabolic processes and neuron-to-neuron synapses. We identified significant hub genes, including TGM2, ITPR1, CHL1, ALDOC, RPS3, FBLN2, NDUFS2, ITGA5, CTNNB1, RBP1, CLSTN2, FABP5, EPHA4, LDHA, and HNRNPL, and analyzed their coexpression and biological functions. TF-gene interaction and TF-miRNA coregulatory network analyses revealed the regulatory relationships of the hub genes. Additional datasets were analyzed to validate hub gene expression, and ALDOC, HNRNPL, and NDUFS2 displayed similar processes in AF and COPD patients. Conclusions: In our study, we demonstrate that metabolic processes and neuron-to-neuron synaptic connections may contribute to the cooccurrence of AF and COPD. The identified hub genes and regulatory networks may act as potential biomarkers and therapeutic targets for these diseases.http://www.sciencedirect.com/science/article/pii/S240584402309638XDifferentially expressed genesAtrial fibrillationchronic obstructive pulmonary diseasehub genesTranscription factor interactions
spellingShingle Shan Xiong
Qiming Liu
Shenghua Zhou
Yichao Xiao
Identification of key genes and regulatory networks involved in the Comorbidity of atrial fibrillation and chronic obstructive pulmonary disease
Heliyon
Differentially expressed genes
Atrial fibrillation
chronic obstructive pulmonary disease
hub genes
Transcription factor interactions
title Identification of key genes and regulatory networks involved in the Comorbidity of atrial fibrillation and chronic obstructive pulmonary disease
title_full Identification of key genes and regulatory networks involved in the Comorbidity of atrial fibrillation and chronic obstructive pulmonary disease
title_fullStr Identification of key genes and regulatory networks involved in the Comorbidity of atrial fibrillation and chronic obstructive pulmonary disease
title_full_unstemmed Identification of key genes and regulatory networks involved in the Comorbidity of atrial fibrillation and chronic obstructive pulmonary disease
title_short Identification of key genes and regulatory networks involved in the Comorbidity of atrial fibrillation and chronic obstructive pulmonary disease
title_sort identification of key genes and regulatory networks involved in the comorbidity of atrial fibrillation and chronic obstructive pulmonary disease
topic Differentially expressed genes
Atrial fibrillation
chronic obstructive pulmonary disease
hub genes
Transcription factor interactions
url http://www.sciencedirect.com/science/article/pii/S240584402309638X
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