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Weighted Gene Co-Expression Network Analysis Identifies Critical Genes in the Development of Heart Failure After Acute Myocardial Infarction
Background: The development of heart failure (HF) remains a common complication following an acute myocardial infarction (AMI), and is associated with substantial adverse outcomes. However, the specific predictive biomarkers and candidate therapeutic targets for post-infarction HF have not been full...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889910/ https://www.ncbi.nlm.nih.gov/pubmed/31850068 http://dx.doi.org/10.3389/fgene.2019.01214 |
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author | Niu, Xiaowei Zhang, Jingjing Zhang, Lanlan Hou, Yangfan Pu, Shuangshuang Chu, Aiai Bai, Ming Zhang, Zheng |
author_facet | Niu, Xiaowei Zhang, Jingjing Zhang, Lanlan Hou, Yangfan Pu, Shuangshuang Chu, Aiai Bai, Ming Zhang, Zheng |
author_sort | Niu, Xiaowei |
collection | PubMed |
description | Background: The development of heart failure (HF) remains a common complication following an acute myocardial infarction (AMI), and is associated with substantial adverse outcomes. However, the specific predictive biomarkers and candidate therapeutic targets for post-infarction HF have not been fully established. We sought to perform a weighted gene co-expression network analysis (WGCNA) to identify key modules, hub genes, and possible regulatory targets involved in the development of HF following AMI. Methods: Genes exhibiting the most (top 50%) variation in expression levels across samples in a GSE59867 dataset were imported to the WGCNA. Gene Ontology and pathway enrichment analyses were performed on genes identified in the key module by Metascape. Gene regulatory networks were constructed using the microarray probe reannotation and bioinformatics database. Hub genes were screened out from the key module and validated using other datasets. Results: A total of 10,265 most varied genes and six modules were identified between AMI patients who developed HF within 6 months of follow-up and those who did not. Specifically, the blue module was found to be the most significantly related to the development of post-infarction HF. Functional enrichment analysis revealed that the blue module was primarily associated with the inflammatory response, immune system, and apoptosis. Seven transcriptional factors, including SPI1, ZBTB7A, IRF8, PPARG, P65, KLF4, and Fos, were identified as potential regulators of the expression of genes identified in the blue module. Further, non-coding RNAs, including miR-142-3p and LINC00537, were identified as having close interactions with genes from the blue module. A total of six hub genes (BCL3, HCK, PPIF, S100A9, SERPINA1, and TBC1D9B) were identified and validated for their predictive value in identifying future HFs. Conclusions: By using the WGCNA, we provide new insights into the underlying molecular mechanism and molecular markers correlated with HF development following an AMI, which may serve to improve risk stratification, therapeutic decisions, and prognosis prediction in AMI patients. |
format | Online Article Text |
id | pubmed-6889910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68899102019-12-17 Weighted Gene Co-Expression Network Analysis Identifies Critical Genes in the Development of Heart Failure After Acute Myocardial Infarction Niu, Xiaowei Zhang, Jingjing Zhang, Lanlan Hou, Yangfan Pu, Shuangshuang Chu, Aiai Bai, Ming Zhang, Zheng Front Genet Genetics Background: The development of heart failure (HF) remains a common complication following an acute myocardial infarction (AMI), and is associated with substantial adverse outcomes. However, the specific predictive biomarkers and candidate therapeutic targets for post-infarction HF have not been fully established. We sought to perform a weighted gene co-expression network analysis (WGCNA) to identify key modules, hub genes, and possible regulatory targets involved in the development of HF following AMI. Methods: Genes exhibiting the most (top 50%) variation in expression levels across samples in a GSE59867 dataset were imported to the WGCNA. Gene Ontology and pathway enrichment analyses were performed on genes identified in the key module by Metascape. Gene regulatory networks were constructed using the microarray probe reannotation and bioinformatics database. Hub genes were screened out from the key module and validated using other datasets. Results: A total of 10,265 most varied genes and six modules were identified between AMI patients who developed HF within 6 months of follow-up and those who did not. Specifically, the blue module was found to be the most significantly related to the development of post-infarction HF. Functional enrichment analysis revealed that the blue module was primarily associated with the inflammatory response, immune system, and apoptosis. Seven transcriptional factors, including SPI1, ZBTB7A, IRF8, PPARG, P65, KLF4, and Fos, were identified as potential regulators of the expression of genes identified in the blue module. Further, non-coding RNAs, including miR-142-3p and LINC00537, were identified as having close interactions with genes from the blue module. A total of six hub genes (BCL3, HCK, PPIF, S100A9, SERPINA1, and TBC1D9B) were identified and validated for their predictive value in identifying future HFs. Conclusions: By using the WGCNA, we provide new insights into the underlying molecular mechanism and molecular markers correlated with HF development following an AMI, which may serve to improve risk stratification, therapeutic decisions, and prognosis prediction in AMI patients. Frontiers Media S.A. 2019-11-26 /pmc/articles/PMC6889910/ /pubmed/31850068 http://dx.doi.org/10.3389/fgene.2019.01214 Text en Copyright © 2019 Niu, Zhang, Zhang, Hou, Pu, Chu, Bai and Zhang http://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 | Genetics Niu, Xiaowei Zhang, Jingjing Zhang, Lanlan Hou, Yangfan Pu, Shuangshuang Chu, Aiai Bai, Ming Zhang, Zheng Weighted Gene Co-Expression Network Analysis Identifies Critical Genes in the Development of Heart Failure After Acute Myocardial Infarction |
title | Weighted Gene Co-Expression Network Analysis Identifies Critical Genes in the Development of Heart Failure After Acute Myocardial Infarction |
title_full | Weighted Gene Co-Expression Network Analysis Identifies Critical Genes in the Development of Heart Failure After Acute Myocardial Infarction |
title_fullStr | Weighted Gene Co-Expression Network Analysis Identifies Critical Genes in the Development of Heart Failure After Acute Myocardial Infarction |
title_full_unstemmed | Weighted Gene Co-Expression Network Analysis Identifies Critical Genes in the Development of Heart Failure After Acute Myocardial Infarction |
title_short | Weighted Gene Co-Expression Network Analysis Identifies Critical Genes in the Development of Heart Failure After Acute Myocardial Infarction |
title_sort | weighted gene co-expression network analysis identifies critical genes in the development of heart failure after acute myocardial infarction |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889910/ https://www.ncbi.nlm.nih.gov/pubmed/31850068 http://dx.doi.org/10.3389/fgene.2019.01214 |
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