Identification of hub genes in chronically hypoxic myocardium using bioinformatics analysis

Wu,Fan; Gao,Feng; He,Siyi; Xiao,Yingbin

doi:10.3892/mmr.2019.10001

Identification of hub genes in chronically hypoxic myocardium using bioinformatics analysis

Authors:
- Fan Wu
- Feng Gao
- Siyi He
- Yingbin Xiao
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Affiliations: Department of Cardiovascular Surgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, P.R. China, Department of Cardiovascular Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P.R. China
Published online on: March 1, 2019 https://doi.org/10.3892/mmr.2019.10001
Pages: 3871-3881
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chronic hypoxia can be observed in the heart under physiological or pathophysiological states, including embryonic development or cyanotic congenital heart disease. The aim of the present study was to examine gene expression profiles of chronically hypoxic myocardium and to explore the pathophysiological mechanisms by which the heart adapts to chronic hypoxia. Raw data from the next‑generation sequencing data set GSE36761 were downloaded from the Gene Expression Omnibus database. The data set comprised 30 specimens, including 8 healthy myocardia and 22 tetralogy of Fallot (TOF) congenital cardiac malformations; only 7 original data sets of healthy myocardia were obtained, and 5/22 TOFs were excluded. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes (DEGs) were performed. Furthermore, network analysis of DEGs using Cytoscape software based on protein‑protein interaction (PPI) data was also conducted. A total of 1,260 DEGs were selected, of which 926 DEGs were enriched in 83 GO biological process terms, including extracellular matrix organization, regeneration and monocyte chemotaxis. Furthermore, 406 DEGs were enriched in 13 KEGG pathways, including cytokine‑cytokine receptor interaction, focal adhesion and apoptosis. PPI network analysis indicated that six hub genes with correlated degree scores >25 among nodes were identified, including G protein subunit β4, C‑C motif chemokine receptor (CCR)1, CCR2, platelet factor 4, catenin β1 and Jun proto‑oncogene (JUN). Of these, JUN was enriched in GO terms of regeneration and neuron projection regeneration, and in KEGG pathways of focal adhesion, apoptosis and Chagas disease (American trypanosomiasis). The present bioinformatics analysis of these DEGs and hub genes may provide a molecular insight to the role of diverse genes in the pathophysiology of chronically hypoxic myocardium and in myocardial adaptation to chronic hypoxia.

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