Comprehensive Analysis of Ferroptosis Markers in Lupus Nephritis Based on Bioinformatics Analysis and Experimental Validation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40823359", "kind": "science-record", "revision": 2, "content_hash": "sha256:99af922bf13bd5dce906f1f873698d407554dca34a4863fcbe7bfa39beac19ef", "created_at": "2026-11-01T20:30:55Z", "updated_at": "2026-11-01T21:35:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive Analysis of Ferroptosis Markers in Lupus Nephritis Based on Bioinformatics Analysis and Experimental Validation.", "doi": "10.2147/JIR.S527545", "pmid": "40823359", "authors": ["Su Zhang", "Weitao Hu", "Chunyan Huang", "Xinxin Lin", "Xiaoqing Chen"], "journal": "Journal of inflammation research", "year": 2025, "abstract": "Introduction: Lupus nephritis (LN) is a common and severe complication of systemic lupus erythematosus (SLE). Ferroptosis is a form of iron-dependent cell death induced by lipid peroxidation. However, its specific role in LN remains unclear.\nMethods: We utilized the GSE32591 obtained from the GEO database to identify differentially expressed genes (DEGs) and conduct enrichment analysis. Differentially expressed ferroptosis-related genes of LN (LNDE-FRGs) were derived by taking the intersection of DEGs and ferroptosis-related genes (FRGs). Three machine learning algorithms were applied to screen candidate key LNDE-FRGs. The expression of the key LNDE-FRGs was validated using external validation cohorts and clinical samples. The diagnostic value of the key LNDE-FRGs was then assessed by receiver operating characteristic curve (ROC) analysis. In addition, we investigated the correlation between the key genes and glomerular filtration rate (GFR), urinary protein and serum creatinine (Scr) in LN patients via the Nephroseq V5 database. Subsequently, we performed immune infiltrating cell analysis of LN kidney tissue using Cibersort. Finally, we validated the expression of the key gene CYBB by clinical samples and in vivo experiments.\nResults: A total of 377 DEGs and 20 LNDE-FRGs were identified. Machine learning algorithms selected four candidate key LNDE-FRGs (CD44, CYBB, TCF4, and PARP12). However, only CYBB exhibited consistent expression trends in both the training and validation cohorts (P < 0.05). Immune infiltration analysis revealed that the expression levels of monocytes and M0 macrophages were significantly higher in the LN group than in the normal control group. In addition, there was a correlation between key genes and GFR, urinary protein and Scr. Finally, the expression level of CYBB was verified in lupus mice.\nConclusion: CYBB may be a ferroptosis-related biomarker in LN. This may provide new ideas for the clinical treatment and pathogenesis of LN.", "claims": [{"id": "claim-method", "statement": "The Student’s t-test was used to compare differences in gene expression between the different groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40823359", "locator": "sections[25] \"Statistical Analysis\" paragraph 2", "quote": "The Student’s t-test was used to compare differences in gene expression between the different groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analysed during the current study are available in the [GEO] repository, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32591].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40823359", "locator": "sections[39] \"Data Sharing Statement\" paragraph 2", "quote": "The datasets generated and/or analysed during the current study are available in the [GEO] repository, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32591]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "However, only CYBB exhibited consistent expression trends in both the training and validation cohorts (P < 0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "However, only CYBB exhibited consistent expression trends in both the training and validation cohorts (P < 0.05)."}, "evidence": [{"asset": "source:pmid:40823359", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "However, only CYBB exhibited consistent expression trends in both the training and validation cohorts (P < 0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "However, only CYBB exhibited consistent expression trends in both the training and validation cohorts (P < 0.05).", "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:40823359"], "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:GSE113342"], "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:GSE113342"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40823359", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/JIR.S527545", "sha256": 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Results: A total of 377 DEGs an", "s the normal control. Sample Acquisition The mice were sacrificed at 16th week. Kidney and blood samples were", "ion Four-week-old female C57BL/6 and MRL/lpr mice were purchased from Fuzhou Wu Laboratory Animal C", "zhou Wu Laboratory Animal Co. Female MRL/lpr mice were selected as the spontaneous lupus mouse mode"], "order_basis": "paper_text_order:1308", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["B with GFR, proteinuria and Scr in LN. (E–G) IHC staining of ACSL4, GPX4 and CYBB in kidney s", "ions. (H) The percentage of positive area in IHC staining. Noted: **** P<0.0001. 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