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Identification of Hub Diagnostic Biomarkers and Candidate Therapeutic Drugs in Heart Failure

PURPOSE: The objective of this study was to identify the potential regulatory mechanisms, diagnostic biomarkers, and therapeutic drugs for heart failure (HF). METHODS: Differentially expressed genes (DEGs) between HF and non-failing donors were screened from the GSE57345, GSE5406, and GSE3586 datase...

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Autores principales: Guo, Yang, Ning, Bobin, Zhang, Qunhui, Ma, Jing, Zhao, Linlin, Lu, QiQin, Zhang, Dejun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8765546/
https://www.ncbi.nlm.nih.gov/pubmed/35058712
http://dx.doi.org/10.2147/IJGM.S349235
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author Guo, Yang
Ning, Bobin
Zhang, Qunhui
Ma, Jing
Zhao, Linlin
Lu, QiQin
Zhang, Dejun
author_facet Guo, Yang
Ning, Bobin
Zhang, Qunhui
Ma, Jing
Zhao, Linlin
Lu, QiQin
Zhang, Dejun
author_sort Guo, Yang
collection PubMed
description PURPOSE: The objective of this study was to identify the potential regulatory mechanisms, diagnostic biomarkers, and therapeutic drugs for heart failure (HF). METHODS: Differentially expressed genes (DEGs) between HF and non-failing donors were screened from the GSE57345, GSE5406, and GSE3586 datasets. Database for Annotation Visualization and Integrated Discovery and Metascape were used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses respectively. The GSE57345 dataset was used for weighted gene co-expression network analysis (WGCNA). The intersecting hub genes from the DEGs and WGCNA were identified and verified with the GSE5406 and GSE3586 datasets. The diagnostic value of the hub genes was calculated through receiver operating characteristic analysis and net reclassification index (NRI). Gene set enrichment analysis (GSEA) was used to filter out the signaling pathways associated with the hub genes. SYBYL 2.1 was used for molecular docking of hub targets and potential HF drugs obtained from the connection map. RESULTS: Functional annotation of the DEGs showed enrichment of negative regulation of angiogenesis, endoplasmic reticulum stress response, and heart development. PTN, LUM, ISLR, and ASPN were identified as the hub genes of HF. GSEA showed that the key genes were related to the transforming growth factor-β (TGF-β) and Wnt signaling pathways. Sirolimus, LY-294002, and wortmannin have been confirmed as potential drugs for HF. CONCLUSION: We identified new hub genes and candidate therapeutic drugs for HF, which are potential diagnostic, therapeutic and prognostic targets and warrant further investigation.
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spelling pubmed-87655462022-01-19 Identification of Hub Diagnostic Biomarkers and Candidate Therapeutic Drugs in Heart Failure Guo, Yang Ning, Bobin Zhang, Qunhui Ma, Jing Zhao, Linlin Lu, QiQin Zhang, Dejun Int J Gen Med Original Research PURPOSE: The objective of this study was to identify the potential regulatory mechanisms, diagnostic biomarkers, and therapeutic drugs for heart failure (HF). METHODS: Differentially expressed genes (DEGs) between HF and non-failing donors were screened from the GSE57345, GSE5406, and GSE3586 datasets. Database for Annotation Visualization and Integrated Discovery and Metascape were used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses respectively. The GSE57345 dataset was used for weighted gene co-expression network analysis (WGCNA). The intersecting hub genes from the DEGs and WGCNA were identified and verified with the GSE5406 and GSE3586 datasets. The diagnostic value of the hub genes was calculated through receiver operating characteristic analysis and net reclassification index (NRI). Gene set enrichment analysis (GSEA) was used to filter out the signaling pathways associated with the hub genes. SYBYL 2.1 was used for molecular docking of hub targets and potential HF drugs obtained from the connection map. RESULTS: Functional annotation of the DEGs showed enrichment of negative regulation of angiogenesis, endoplasmic reticulum stress response, and heart development. PTN, LUM, ISLR, and ASPN were identified as the hub genes of HF. GSEA showed that the key genes were related to the transforming growth factor-β (TGF-β) and Wnt signaling pathways. Sirolimus, LY-294002, and wortmannin have been confirmed as potential drugs for HF. CONCLUSION: We identified new hub genes and candidate therapeutic drugs for HF, which are potential diagnostic, therapeutic and prognostic targets and warrant further investigation. Dove 2022-01-14 /pmc/articles/PMC8765546/ /pubmed/35058712 http://dx.doi.org/10.2147/IJGM.S349235 Text en © 2022 Guo et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Guo, Yang
Ning, Bobin
Zhang, Qunhui
Ma, Jing
Zhao, Linlin
Lu, QiQin
Zhang, Dejun
Identification of Hub Diagnostic Biomarkers and Candidate Therapeutic Drugs in Heart Failure
title Identification of Hub Diagnostic Biomarkers and Candidate Therapeutic Drugs in Heart Failure
title_full Identification of Hub Diagnostic Biomarkers and Candidate Therapeutic Drugs in Heart Failure
title_fullStr Identification of Hub Diagnostic Biomarkers and Candidate Therapeutic Drugs in Heart Failure
title_full_unstemmed Identification of Hub Diagnostic Biomarkers and Candidate Therapeutic Drugs in Heart Failure
title_short Identification of Hub Diagnostic Biomarkers and Candidate Therapeutic Drugs in Heart Failure
title_sort identification of hub diagnostic biomarkers and candidate therapeutic drugs in heart failure
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8765546/
https://www.ncbi.nlm.nih.gov/pubmed/35058712
http://dx.doi.org/10.2147/IJGM.S349235
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