Integrated Bioinformatics and Experimental Validation Reveal Macrophage Polarization-Related Biomarkers for Osteoarthritis Diagnosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40765736", "kind": "science-record", "revision": 4, "content_hash": "sha256:3899fe1e725a942cb23a45014e4c2a93852291dbc752c8da794b33f85033c03e", "created_at": "2026-11-01T20:30:51Z", "updated_at": "2026-11-01T22:56:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated Bioinformatics and Experimental Validation Reveal Macrophage Polarization-Related Biomarkers for Osteoarthritis Diagnosis.", "doi": "10.2147/JMDH.S537507", "pmid": "40765736", "authors": ["Qiwang He", "Lingling Liu", "Xinyu Hu", "Lixia Lin", "Zhenyu Song", "Yuyang Xia", "Qianming Lin", "Jihua Wei", "Shanlang Li"], "journal": "Journal of multidisciplinary healthcare", "year": 2025, "abstract": "Purpose: Osteoarthritis (OA) is the most common type of arthritis and early detection is crucial to improving prognosis. In this study, we identified crucial genes associated with macrophage polarization in OA and constructed a diagnostic model to provide novel insights for diagnostic and therapeutic strategies.\nMethods: The GSE55235 and GSE55457 datasets were merged through the GEO database to identify genes related to macrophage polarization by conducting weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machine recursive feature elimination (SVM-RFE) algorithms were used to identify hub genes and construct a diagnostic model validated through internal datasets and multiple external bulk RNA-seq and single-cell RNA-seq data. Additionally, various analyses, including immune infiltration, gene set enrichment analysis, competing endogenous RNA (ceRNA) construction, and drug prediction, were conducted. Finally, clinical samples were clinically validated through RT-qPCR (OA: Control = 10: 5) and IHC (6: 5) experiments.\nResults: Three hub genes (MYC, SIK1, and NFIL3) were identified, and the diagnostic model constructed using them demonstrated good diagnostic efficacy in both internal and external datasets (internal AUC = 0.965, external AUC = 0.847). In vitro experiments revealed that the hub genes in the synovial tissue of OA patients were significantly down-regulated (P < 0.01), confirming their potential as diagnostic biomarkers.\nConclusion: We constructed an OA diagnostic model related to macrophage polarization through comprehensive bioinformatics analysis, and the results indicated that these genes have high diagnostic value. However, further clinical studies and experimental assessments are needed to validate these findings.", "claims": [{"id": "claim-method", "statement": "The “limma” package was utilized to analyze DEGs, with the differential screening criteria: | log2FC | > 2.0, adj. P < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40765736", "locator": "sections[3] \"Data Collection and Processing\" paragraph 4", "quote": "The “limma” package was utilized to analyze DEGs, with the differential screening criteria: | log2FC | > 2.0, adj. P < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "This study analyzed publicly available datasets. These data can be found here: National Center for Biotechnology Information (NCBI), Gene Expression Omnibus (GEO), https://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40765736", "locator": "sections[39] \"Data Sharing Statement\" paragraph 2", "quote": "This study analyzed publicly available datasets. These data can be found here: National Center for Biotechnology Information (NCBI), Gene Expression Omnibus (GEO), https://www.ncbi.nlm.nih.gov/geo/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A macrophage-polarization-related OA diagnostic model based on MYC, SIK1, and NFIL3 achieved an internal AUC of 0.965 and an external AUC of 0.847.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40765736", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Three hub genes (MYC, SIK1, and NFIL3) were identified, and the diagnostic model constructed using them demonstrated good diagnostic efficacy in both internal and external datasets (internal AUC = 0.965, external AUC = 0.847)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A macrophage-polarization-related OA diagnostic model based on MYC, SIK1, and NFIL3 achieved an internal AUC of 0.965 and an external AUC of 0.847.", "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:40765736"], "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:GSE152805"], "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:GSE152805"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40765736", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/JMDH.S537507", "sha256": "sha256:5b0f98217bcaf35017073b2e4c123a2cf51a93f25c5fe03264cd3405849c4271", "bytes": 65637, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/JMDH.S537507", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12323875", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE152805", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152805", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE152805", "version": null, "note": "This study analyzed publicly available datasets. 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