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Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy
BACKGROUND: Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. DCM is a disease of the heart muscle and is characterized by enlargement and dilation of at least one ventricle alo...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157606/ https://www.ncbi.nlm.nih.gov/pubmed/35702326 http://dx.doi.org/10.4330/wjc.v14.i5.282 |
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author | Liu, Zhou Song, Ying-Nan Chen, Kai-Yuan Gao, Wei-Long Chen, Hong-Jin Liang, Gui-You |
author_facet | Liu, Zhou Song, Ying-Nan Chen, Kai-Yuan Gao, Wei-Long Chen, Hong-Jin Liang, Gui-You |
author_sort | Liu, Zhou |
collection | PubMed |
description | BACKGROUND: Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. DCM is a disease of the heart muscle and is characterized by enlargement and dilation of at least one ventricle alongside impaired contractility with left ventricular ejection fraction < 40%. It is also associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. However, the pathogenesis and potential biomarkers of DCM remain to be investigated. AIM: To investigate the candidate genes and pathways involved in DCM patients. METHODS: Two expression datasets (GSE3585 and GSE5406) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between the DCM patients and healthy individuals were identified using the R package “linear models for microarray data.” The pathways with common DEGs were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analyses. Moreover, a protein-protein interaction network (PPI) was constructed to identify the hub genes and modules. The MicroRNA Database was applied to predict the microRNAs (miRNAs) targeting the hub genes. Additionally, immune cell infiltration in DCM was analyzed using CIBERSORT. RESULTS: In total, 97 DEGs (47 upregulated and 50 downregulated) were identified. GO analysis showed that the DEGs were mainly enriched in “response to growth factor,” “extracellular matrix,” and “extracellular matrix structural constituent.” KEGG pathway analysis indicated that the DEGs were mainly enriched in “protein digestion and absorption” and “interleukin 17 (IL-17) signaling pathway.” The PPI network suggested that collagen type III alpha 1 chain (COL3A1) and COL1A2 contribute to the pathogenesis of DCM. Additionally, visualization of the interactions between miRNAs and the hub genes revealed that hsa-miR-5682 and hsa-miR-4500 interacted with both COL3A1 and COL1A2, and thus these miRNAs might play roles in DCM. Immune cell infiltration analysis revealed that DCM patients had more infiltrated plasma cells and fewer infiltrated B memory cells, T follicular helper cells, and resting dendritic cells. CONCLUSION: COL1A2 and COL3A1 and their targeting miRNAs, hsa-miR-5682 and hsa-miR-4500, may play critical roles in the pathogenesis of DCM, which are closely related to the IL-17 signaling pathway and acute inflammatory response. These results may provide useful clues for the diagnosis and treatment of DCM. |
format | Online Article Text |
id | pubmed-9157606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-91576062022-06-13 Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy Liu, Zhou Song, Ying-Nan Chen, Kai-Yuan Gao, Wei-Long Chen, Hong-Jin Liang, Gui-You World J Cardiol Basic Study BACKGROUND: Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. DCM is a disease of the heart muscle and is characterized by enlargement and dilation of at least one ventricle alongside impaired contractility with left ventricular ejection fraction < 40%. It is also associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. However, the pathogenesis and potential biomarkers of DCM remain to be investigated. AIM: To investigate the candidate genes and pathways involved in DCM patients. METHODS: Two expression datasets (GSE3585 and GSE5406) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between the DCM patients and healthy individuals were identified using the R package “linear models for microarray data.” The pathways with common DEGs were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analyses. Moreover, a protein-protein interaction network (PPI) was constructed to identify the hub genes and modules. The MicroRNA Database was applied to predict the microRNAs (miRNAs) targeting the hub genes. Additionally, immune cell infiltration in DCM was analyzed using CIBERSORT. RESULTS: In total, 97 DEGs (47 upregulated and 50 downregulated) were identified. GO analysis showed that the DEGs were mainly enriched in “response to growth factor,” “extracellular matrix,” and “extracellular matrix structural constituent.” KEGG pathway analysis indicated that the DEGs were mainly enriched in “protein digestion and absorption” and “interleukin 17 (IL-17) signaling pathway.” The PPI network suggested that collagen type III alpha 1 chain (COL3A1) and COL1A2 contribute to the pathogenesis of DCM. Additionally, visualization of the interactions between miRNAs and the hub genes revealed that hsa-miR-5682 and hsa-miR-4500 interacted with both COL3A1 and COL1A2, and thus these miRNAs might play roles in DCM. Immune cell infiltration analysis revealed that DCM patients had more infiltrated plasma cells and fewer infiltrated B memory cells, T follicular helper cells, and resting dendritic cells. CONCLUSION: COL1A2 and COL3A1 and their targeting miRNAs, hsa-miR-5682 and hsa-miR-4500, may play critical roles in the pathogenesis of DCM, which are closely related to the IL-17 signaling pathway and acute inflammatory response. These results may provide useful clues for the diagnosis and treatment of DCM. Baishideng Publishing Group Inc 2022-05-26 2022-05-26 /pmc/articles/PMC9157606/ /pubmed/35702326 http://dx.doi.org/10.4330/wjc.v14.i5.282 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/ |
spellingShingle | Basic Study Liu, Zhou Song, Ying-Nan Chen, Kai-Yuan Gao, Wei-Long Chen, Hong-Jin Liang, Gui-You Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy |
title | Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy |
title_full | Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy |
title_fullStr | Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy |
title_full_unstemmed | Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy |
title_short | Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy |
title_sort | bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157606/ https://www.ncbi.nlm.nih.gov/pubmed/35702326 http://dx.doi.org/10.4330/wjc.v14.i5.282 |
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