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pmid:37609434
Identification of hub genes associated with oxidative stress in heart failure and their correlation with immune infiltration using bioinformatics analysis.
Jianjun Gu · Li Na Zhang · Xiang Gu · Ye Zhu
PeerJ · 2023 doi:10.7717/peerj.15893
Paper
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Experiment
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Data
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Analysis
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Complete file
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In this study, our aim was to identify the hub genes associated with oxidative stress andimmune infiltration of HF by bioinformatics analysis and experimental verification. The expression profile of GSE36074 was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened by GEO2R. The genes related to oxidative stress were extracted from GeneCards websites. Then, the functional enrichment analysis of oxidative stress-related DEGs (OSRDEGs) was performed using DAVID. In addition, we constructed a protein-protein interaction (PPI) network using the STRING database and screened for hub genes with Cytoscape software. We also used CIBERSORTx to analyze immune infiltration in mice heart tissues between the TAC and Sham groups and explored the correlation between immune cells and hub genes. Finally, the hub genes were carried out using reverse transcription quantitative PCR (RT-qPCR), immunohistochemistry (IHC) and western blot. A total of 136 OSRDEGs were found in GSE36074. Enrichment analysis revealed that these OSRDEGs were enriched in the mitochondrion, HIF-1, FoxO, MAPK and TNF signaling pathway. The five hub genes (Mapk14, Hif1a, Myc, Hsp90ab1, and Hsp90aa1) were screened by the cytoHubba plugin. The correlation analysis between immune cells and hub genes showed that Mapk14 was positively correlated with Th2 Cells, while Hif1a and Hsp90ab1exhibited a negative correlation with Th2 Cells; Myc exhibited a negative correlation with Monocytes; whereas, Hsp90aa1 was negatively correlated with NK Resting. Finally, five hub genes were validated by RT-qPCR, IHC and western blot. Mapk14, Hif1a, Myc, Hsp90ab1, and Hsp90aa1 are hub genes of HF and may play a critical role in the oxidative stress of HF. This study may provide new targets for the treatment of HF, and the potential immunotherapies are worthy of further study.", "claims": [{"id": "claim-method", "statement": "GEO2R online tool was used to screen the DEGs and oxidative stress-related genes (OSRGs) were extracted from the GeneCards website. DEGs were defined based on |Fold change |≥ 1 and adj.p-value of < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37609434", "locator": "sections[4] \"Identification of oxidative stress-related differential genes\" paragraph 2", "quote": "GEO2R online tool was used to screen the DEGs and oxidative stress-related genes (OSRGs) were extracted from the GeneCards website. DEGs were defined based on |Fold change |≥ 1 and adj.p-value of < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:The data are available in the Supplemental Files and at NCBI GEO: GSE36074.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37609434", "locator": "sections[29] \"Data Availability\" paragraph 2", "quote": "The following information was supplied regarding data availability:The data are available in the Supplemental Files and at NCBI GEO: GSE36074."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 136 OSRDEGs were found in GSE36074.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37609434", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A total of 136 OSRDEGs were found in GSE36074."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "A total of 136 OSRDEGs were found in GSE36074.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37609434"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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