Bioinformatics identification and validation of pyroptosis-related gene for ischemic stroke.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40091022", "kind": "science-record", "revision": 3, "content_hash": "sha256:7092ed08c07c7de097dc70e5d38a50c489240df18300368bedaef975c7e4cb23", "created_at": "2026-11-01T20:30:18Z", "updated_at": "2026-11-01T22:13:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics identification and validation of pyroptosis-related gene for ischemic stroke.", "doi": "10.1186/s12920-025-02119-2", "pmid": "40091022", "authors": ["Xinying Shang", "Rui Wei", "Di Yang", "Bawei Yu", "Wei Zhang"], "journal": "BMC medical genomics", "year": 2025, "abstract": "BACKGROUND: Ischemic stroke (IS) is one of the common and frequent diseases with extremely high lethality and disability in the world, and there is no effective treatment at present. This study aimed to screen hub genes involved in cerebral ischemia/reperfusion injury (CIRI) and pyroptosis, and explore promising intervention targets.\nMETHODS: CIRI-related genes (GSE202659 and GSE131193) and pyroptosis-related genes (PRGs) in mice were obtained from the Gene Expression Omnibus (GEO) and GeneCards database. We screened for LASSO regression to construct a prognostic model of GSE131193 and PRGs and examined by GSE137482. The functional enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed on pyroptosis-related differentially expressed genes (PRDEGs) of GSE202659.The key modules for CIRI and pyroptosis were identified by Weight Gene Co-expression Network Analysis (WGCNA). Subsequently, Protein-protein Interaction (PPI) network and the Cytoscape was constructed to screen out hub genes. Used the starBase to predict miRNA interacting with hub genes and constructed mRNA-miRNA-lncRNA interaction networks. CIRI-related Molecular Subtypes were constructed for hub genes. The relationship between immune cells and hub genes was verified via CIBERSORT. Finally, we selected C57BL/6 mice to construct models to confirm hub genes by enzyme linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), western blot, and Immunofluorescence.\nRESULTS: A total of 272 PRGs and 35 PRDEGs were screened. An eight-gene risk prediction models were established (AUC = 0.868). GO, KEGG, GSEA and GSVA analyses revealed that PRDEGs were mainly involved in positive regulation of cytokine production, and NOD-like receptor signaling pathway. And then, seven hub genes (Irf1, Icam1, Tlr2, Tnf, Cebpb, Il1rn, and Casp8) were identified by PPI. Icam1, Tnf, Cebpb, Il1rn, and Casp8 had high expression profiles in Cluster2 by hierarchical clustering. The immune infiltration analysis results showed that among the hub genes, Cebpb, Il1rn, and Casp8, showed a significant positive correlation with the degree of NK.Actived, and Icam1 showed a significant negative correlation with B.Cells.Memory. The results of animal experiments significantly demonstrated an upregulation of Irf1, Icam1, Tlr2, Cebpb, and Il1rn.\nCONCLUSION: Our finding indicated that Irf1, Icam1, Tlr2, Cebpb, and Il1rn are hub genes associated with pyroptosis, and these genes are all associated with different immune cells, so as to provide new targets for the prevention and treatment of IS from the perspective of pyroptosis.", "claims": [{"id": "claim-method", "statement": "We performed WGCNA (Version 1.70-3) analysis on GSE131193, constructed a PRG-based co-expression network, obtained modules and genes associated with the CIRI phenotype.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40091022", "locator": "sections[7] \"Screening and correlation analysis of hub genes\" paragraph 2", "quote": "We performed WGCNA (Version 1.70-3) analysis on GSE131193, constructed a PRG-based co-expression network, obtained modules and genes associated with the CIRI phenotype."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets supporting the conclusions of this article are included within the article and its Additional files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40091022", "locator": "sections[34] \"notes\" paragraph 1", "quote": "The datasets supporting the conclusions of this article are included within the article and its Additional files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Irf1, Icam1, Tlr2, Cebpb, and Il1rn were identified as hub genes associated with pyroptosis and different immune cells, providing potential targets for ischemic stroke prevention and treatment.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40091022", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our finding indicated that Irf1, Icam1, Tlr2, Cebpb, and Il1rn are hub genes associated with pyroptosis, and these genes are all associated with different immune cells, so as to provide new targets for the prevention and treatment of IS from the perspective of pyroptosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Irf1, Icam1, Tlr2, Cebpb, and Il1rn were identified as hub genes associated with pyroptosis and different immune cells, providing potential targets for ischemic stroke prevention and treatment.", "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:40091022"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE131193"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE131193"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40091022", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12920-025-02119-2", "sha256": 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RESULTS: A total of"], "order_basis": "paper_text_order:1611", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["e chain reaction (RT-PCR), western blot, and Immunofluorescence. RESULTS: A total of 272 PRGs and 35 PRDEGs"], "order_basis": "paper_text_order:1629", "id": "assay:3"}, {"role": "analysis", "definition_id": "clustering", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["hierarchical_cluster"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["hierarchical clustering"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}