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pmid:35923893
Screening of ferroptosis-related genes in sepsis-induced liver failure and analysis of immune correlation.
Qingli Chen · Luxiang Liu · Shuangling Ni
PeerJ · 2022 doi:10.7717/peerj.13757
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Experiment
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Analysis
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Complete file
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Our research aims to screen ferroptosis-related genes in sepsis-induced liver failure as targeted therapy for patients with liver failure.\nMethods: Using the limma software, we analyzed the differentially expressed genes (DEGs) in the GSE60088 dataset downloaded from the Gene Expression Omnibus (GEO) database. Clusterprofiler was applied for enrichment analysis of DEGs enrichment function. Then, the ferroptosis-related genes of the mice in the FerrDb database were crossed with DEGs. Sepsis mice model were prepared by cecal ligation and perforation (CLP). ALT and AST in the serum of mice were measured using detection kit. The pathological changes of the liver tissues in mice were observed by hematoxylin-eosin (H & E) staining. We detected the apoptosis of mice liver tissues using TUNEL. The expression of Hmox1, Epas1, Sirt1, Slc3a2, Jun, Plin2 and Zfp36 were detected by qRT-PCR.\nResults: DEGs analysis showed 136 up-regulated and 45 down-regulated DEGs. Meanwhile, we found that the up-regulated DEGs were enriched in pathways including the cytokine biosynthesis process while the down-regulated DEGs were enriched in pathways such as organic hydroxy compound metabolic process. In this study, seven genes (Hmox1, Epas1, Sirt1, Slc3a2, Jun, Plin2 and Zfp36) were obtained through the intersection of FerrDb database and DEGs. However, immune infiltration analysis revealed that ferroptosis-related genes may promote the development of liver failure through B cells and natural killer (NK) cells. Finally, it was confirmed by the construction of septic liver failure mice model that ferroptosis-related genes of Hmox1, Slc3a2, Jun and Zfp36 were significantly correlated with liver failure and were highly expressed.\nConclusion: The identification of ferroptosis-related genes Hmox1, Slc3a2, Jun and Zfp36 in the present study contribute to our understanding of the molecular mechanism of sepsis-induced liver failure, and provide candidate targets for the diagnosis and treatment of the disease.", "claims": [{"id": "claim-method", "statement": "We performed differential gene expression analysis of the liver failure in the GSE60088 dataset using the limma (Version: 3.42.2) software package (Ritchie et al., 2015), and the Volcano plot and heatmap were correspondingly drawn.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35923893", "locator": "sections[4] \"DEGs analysis\" paragraph 2", "quote": "We performed differential gene expression analysis of the liver failure in the GSE60088 dataset using the limma (Version: 3.42.2) software package (Ritchie et al., 2015), and the Volcano plot and heatmap were correspondingly drawn."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available at GEO: GSE60088 and the FerrDb database (http://www.zhounan.org/ferrdb/legacy/operations/download.html).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35923893", "locator": "sections[24] \"Additional Information and Declarations\" paragraph 5", "quote": "The datasets used and/or analyzed during the current study are available at GEO: GSE60088 and the FerrDb database (http://www.zhounan.org/ferrdb/legacy/operations/download.html)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Seven ferroptosis-related genes were identified, and Hmox1, Slc3a2, Jun and Zfp36 were confirmed as significantly correlated with and highly expressed in sepsis-induced liver failure.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35923893", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In this study, seven genes (Hmox1, Epas1, Sirt1, Slc3a2, Jun, Plin2 and Zfp36) were obtained through the intersection of FerrDb database and DEGs."}, {"asset": "source:pmid:35923893", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Finally, it was confirmed by the construction of septic liver failure mice model that ferroptosis-related genes of Hmox1, Slc3a2, Jun and Zfp36 were significantly correlated with liver failure and were highly expressed."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Seven ferroptosis-related genes were identified, and Hmox1, Slc3a2, Jun and Zfp36 were confirmed as significantly correlated with and highly expressed in sepsis-induced liver failure.", "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:35923893"], "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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(C) The apoptosis in the liver tissues of mice detected by TUN"], "order_basis": "paper_text_order:951", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["We performed differential gene expression analysis of the liver failure in the GSE60088 dataset using the limma (Version: 3.42.2) software package (Ritchie et al., 2015), and the Volcano plot and heatmap were correspondingly drawn."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}