NCF2 as a Novel Diagnostic Biomarker in Ulcerative Colitis: Linking Macrophage Infiltration to Immune Dysregulation via Multi-Omics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41368353", "kind": "science-record", "revision": 3, "content_hash": "sha256:4a680af8411b26d34ad5aaefb48f8590d919da38fdbdfbe58121f1ef94f7116e", "created_at": "2026-11-01T20:31:22Z", "updated_at": "2026-11-01T22:15:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "NCF2 as a Novel Diagnostic Biomarker in Ulcerative Colitis: Linking Macrophage Infiltration to Immune Dysregulation via Multi-Omics Analysis.", "doi": "10.2147/JIR.S552678", "pmid": "41368353", "authors": ["Fang Zhang", "Jianwei Zhu", "Haiyan Liu", "Jianlan Ye", "Yuanyuan Li", "Bingcheng Wang"], "journal": "Journal of inflammation research", "year": 2025, "abstract": "Background: Ulcerative colitis (UC) is a debilitating inflammatory condition with growing global prevalence. While immune dysregulation is a known hallmark, the specific molecular drivers and their link to fibrosis remain incompletely characterized. To address this, we conducted a study combining bioinformatic analyses of public datasets with experimental validation to identify and validate key biomarker candidates involved in UC pathogenesis.\nMethods: Three publicly available ulcerative colitis gene expression datasets (GSE38713, GSE87466, GSE119600) were retrieved from the Gene Expression Omnibus (GEO). Immune cell infiltration was evaluated using ssGSEA, with significant cell types identified by Wilcoxon test and LASSO regression. DEGs were screened and analyzed using GO, KEGG, and PPI networks. Hub genes were identified using cytoHubba and validated via ROC curves. RT-qPCR, WB, and IHC validated findings in UC rat models and clinical samples.\nResults: The differentially expressed genes (DEGs) were evaluated using ten distinct algorithms, resulting in the identification of eight common DEGs following an intersection analysis. 4 hub genes were further identified through validation using the GSE119600 dataset, namely Cluster of Differentiation 274 (CD274), Matrix Metallopeptidase 1 (MMP1), neutrophil cytosolic factor 2 (NCF2), Plasminogen Activator Urokinase (PLAU). Notably, NCF2 demonstrated the highest specificity and sensitivity for diagnosing ulcerative colitis (UC), suggesting its potential utility as a diagnostic biomarker. Additionally, a distinct immune cell type exhibited significant differences between UC patients and healthy controls (HC). Correlation analyses utilizing bioinformatics techniques revealed that the hub genes CD274, MMP1, NCF2, and PLAU were positively associated with macrophage infiltration, highlighting their potential role in the immune response in UC.\nConclusion: CD274, MMP1, NCF2, PLAU can serve as hub genes associated with UC. Among these, NCF2 stands out as a particularly promising target for further research into the underlying mechanisms of UC. Additionally, NCF2 may play a role in the development and progression of UC by modulating macrophage infiltration.", "claims": [{"id": "claim-method", "statement": "For receiver operating characteristic (ROC) analysis, the “pROC” package was employed, and visualizations were created using “ggplot2.” The area under the curve (AUC) was computed to evaluate the diagnostic potential of UC biomarkers.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41368353", "locator": "sections[9] \"Analyzing the Diagnostic Validity of Biomarkers\" paragraph 2", "quote": "For receiver operating characteristic (ROC) analysis, the “pROC” package was employed, and visualizations were created using “ggplot2.” The area under the curve (AUC) was computed to evaluate the diagnostic potential of UC biomarkers."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available in the GEO repository, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38713, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE92415, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87466, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119600.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41368353", "locator": "sections[29] \"Data Sharing Statement\" paragraph 2", "quote": "The datasets generated and/or analyzed during the current study are available in the GEO repository, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38713, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE92415, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87466, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119600."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ROC analysis using GSE119600 identified NCF2 as the strongest individual diagnostic biomarker for ulcerative colitis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41368353", "locator": "sections[9] \"Analyzing the Diagnostic Validity of Biomarkers\" paragraph 2", "quote": "For receiver operating characteristic (ROC) analysis, the “pROC” package was employed, and visualizations were created using “ggplot2.”"}, {"asset": "source:pmid:41368353", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Notably, NCF2 demonstrated the highest specificity and sensitivity for diagnosing ulcerative colitis (UC), suggesting its potential utility as a diagnostic biomarker."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "ROC analysis using GSE119600 identified NCF2 as the strongest individual diagnostic biomarker for ulcerative colitis.", "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:41368353"], "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:GSE119600"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE119600"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41368353", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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Each experiment was independent", "sion levels in the normal and UC groups (E); Immunohistochemical staining of NCF2 protein in normal mouse col"], "order_basis": "paper_text_order:996", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["T-qPCR, WB, and IHC validated findings in UC rat models and clinical samples. Results: The di", "(Figure 11E–G) corroborated results from the mouse model, aligning with qPCR and Western blot data. 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