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Published on: January 28, 2020
Bioinformatics Analysis Reveals Hub Genes That May Reduce Inflammation and Complications After Cardiopulmonary Bypass
Quan Qi1, Yibo Yan2, Cheng Luo3
1Department of Cardiac Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. drqiquan0213@163.com.
Insights
This study identified FOS, JUN, ATF3, and EGR1 as key genes potentially mitigating inflammation and complications following cardiopulmonary bypass (CPB) surgery. These genes and the AP-1 pathway may offer therapeutic targets for improving patient outcomes after cardiac procedures.
Area of Science:
- Molecular Biology
- Bioinformatics
- Cardiovascular Surgery
Background:
- Cardiopulmonary bypass (CPB) is essential for cardiac surgery but causes adverse inflammatory effects.
- Identifying genetic factors that can reduce CPB-induced inflammation is crucial for improving patient outcomes.
Purpose of the Study:
- To identify genes and pathways involved in the inflammatory response and complications after CPB.
- To investigate the role of FOS, JUN, ATF3, and EGR1 in CPB-associated inflammation.
Main Methods:
- Utilized the GSE132176 dataset from the Gene Expression Omnibus (GEO) database.
- Performed differential gene expression analysis, protein-protein interaction network analysis (using STRING and Cytoscape), and enrichment analysis.
- Validated key gene expression levels using quantitative real-time PCR (qRT-PCR).
Main Results:
- Identified 72 differentially expressed genes (DEGs), including two functional and one hub gene module.
- FOS and ATF3 modular genes were enriched in specific signaling pathways (NGF-stimulated transcription, AP1 pathway, cytomegalovirus infection).
- FOS, JUN, ATF3, and EGR1 emerged as critical hub genes, primarily involved in the AP-1 pathway.
Conclusions:
- FOS, JUN, ATF3, and EGR1, along with the AP-1 pathway, are implicated in CPB-induced inflammation and complications.
- These genes represent potential therapeutic targets for mitigating adverse effects of CPB.
- Bioinformatic findings were corroborated by experimental validation through qRT-PCR.
Abstract:
Cardiopulmonary bypass (CPB), though indispensable in many cardiac surgery procedures, has several undesirable consequences. The aim of this study was to identify potential genes that may reduce the inflammatory response and complications after CPB. The GSE132176 dataset was selected from the Gene Expression Omnibus (GEO) database and included 10 patients with tetralogy of Fallot and 10 patients with an atrial septal defect who underwent CPB surgery. TSV files were downloaded after GEO2R processing. Protein-protein interaction analysis of common differentially expressed genes (DEGs) was performed using the Search Tool for the Retrieval of Interacting Genes. Gene modules and hub genes were visualized in the protein-protein interaction network using Cytoscape. Enrichment analysis was performed for all important DEGs, modular genes, and hub genes. A total of 72 DEGs were screened, including two functional and one hub gene module. FOS modular genes were primarily enriched in NGF-stimulated transcription, spinal cord injury, and PID AP1 pathway. The ATF3 modular gene was mainly enriched in cytomegalovirus infection and transcriptional misregulation in cancer. Hub gene modules were primarily enriched in the PID AP1 pathway, positive regulation of pri-miRNA transcription by RNA polymerase II, and the PID ATF2 pathway. FOS, JUN, ATF3, and EGR1 were the four most important hub genes; the top three hub genes were involved in the formation of AP-1 and enriched in the AP-1 pathway. Finally, we measured the expression levels of these four genes in patients undergoing CPB via qRT-PCR, and the results were consistent with those obtained in bioinformatic analysis. FOS, JUN, ATF3, and EGR1 and the AP-1 pathway may play key roles in inflammation and complications caused by CPB.
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