Exploration of key genes associated with oxidative stress in polycystic ovary syndrome and experimental validation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40083347", "kind": "science-record", "revision": 3, "content_hash": "sha256:d3fe0747b93f80bc8080ae570537e72386872f65a35435f7b16d6410c532e48e", "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": "Exploration of key genes associated with oxidative stress in polycystic ovary syndrome and experimental validation.", "doi": "10.3389/fmed.2025.1493771", "pmid": "40083347", "authors": ["Qinhua Li", "Lei Liu", "Yuhan Liu", "Tingting Zheng", "Ningjing Chen", "Peiyao Du", "Hong Ye"], "journal": "Frontiers in medicine", "year": 2025, "abstract": "Introduction: The current study demonstrated that oxidative stress (OS) is closely related to the pathogenesis of polycystic ovary syndrome (PCOS). However, there are numerous factors that lead to OS, therefore, identifying the key genes associated with PCOS that contribute to OS is crucial for elucidating the pathogenesis of PCOS and selecting appropriate treatment strategies.\nMethods: Four datasets (GSE95728, GSE106724, GSE138572, and GSE145296) were downloaded from the gene expression omnibus (GEO) database. GSE95728 and GSE106724 were combined to identify differentially expressed genes (DEGs) in PCOS. weighted gene correlation network analysis (WGCNA) was used to screen key module genes associated with PCOS. Differentially expressed OS related genes (DE-OSRGs) associated with PCOS were obtained by overlapping DEGs, key module genes, and OSRGs. Subsequently, the optimal machine model was obtained to identify key genes by comparing the performance of the random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM). The molecular networks were constructed to reveal the non-coding regulatory mechanisms of key genes based on GSE138572 and GSE145296. The Drug-Gene Interaction Database (DGIdb) was used to predict the potential therapeutic agents of key genes for PCOS. Finally, the expression of key OSRGs was validated by RT-PCR.\nResults: In this study, 8 DE-OSRGs were identified. Based on the residuals and root mean square error of the three models, the best performance of RF was derived and 7 key genes (TNFSF10, CBL, IFNG, CP, CASP8, APOA1, and DDIT3) were identified. The GSEA enrichment analysis revealed that TNFSF10, CP, DDIT3, and INFG are all enriched in the NOD-like receptor signaling pathway and natural killer cell-mediated cytotoxicity pathways. The molecular regulatory network uncovered that both TNFSF10 and CBL are regulated by non-coding RNAs. Additionally, 70 potential therapeutic drugs for PCOS were predicted, with ibuprofen associated with DDIT3 and IFNG. RT-qPCR validation confirmed the expression trends of key genes IFNG, DDIT3, and APOA1 were consistent with the dataset, and the observed differences were statistically significant (P < 0.05).\nConclusion: The identification of seven key genes and molecular regulatory networks through bioinformatics analysis is of great significance for exploring the pathogenesis and therapeutic strategies of PCOS.", "claims": [{"id": "claim-method", "statement": "Further, the RF model had the smallest sample residuals and was treated as the optimal model (Figures 4A, B).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40083347", "locator": "sections[18] \"3.4 Identification of key genes\" paragraph 2", "quote": "Further, the RF model had the smallest sample residuals and was treated as the optimal model (Figures 4A, B)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in this article/Supplementary material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40083347", "locator": "sections[29] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in this article/Supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Based on the residuals and root mean square error of the three models, the best performance of RF was derived and 7 key genes (TNFSF10, CBL, IFNG, CP, CASP8, APOA1, and DDIT3) were identified.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40083347", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Based on the residuals and root mean square error of the three models, the best performance of RF was derived and 7 key genes (TNFSF10, CBL, IFNG, CP, CASP8, APOA1, and DDIT3) were identified."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Based on the residuals and root mean square error of the three models, the best performance of RF was derived and 7 key genes (TNFSF10, CBL, IFNG, CP, CASP8, APOA1, and DDIT3) were identified.", "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:40083347"], "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:GSE106724"], "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:machine_learning_random_forest", "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:GSE106724"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:machine_learning_random_forest"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40083347", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmed.2025.1493771", "sha256": "sha256:f3f24cd5b2655c6c457951efcdc70e4c35141dd6dd09d1d8e95f751a1facfbdf", "bytes": 57438, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmed.2025.1493771", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11904916", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE106724", "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=GSE106724", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE106724", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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RT-qPCR validation confirmed the expression trends o", "ibuprofen associated with DDIT3 and IFNG. RT-qPCR validation confirmed the expression trends o", "evels of key genes in clinical samples using RT-qPCR. TNFSF10, IFNG, CASP8, and DDIT3 all exhibit", "ls of key genes in clinical samples using RT-qPCR. TNFSF10, IFNG, CASP8, and DDIT3 all exhibit"], "order_basis": "paper_text_order:2108", "id": "assay:1"}, {"role": "analysis", "definition_id": "machine_learning", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Further, the RF model had the smallest sample residuals and was treated as the optimal model (Figures 4A, B)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}