Identification and validation of ferroptosis-related hub genes in obstructive sleep apnea syndrome.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36937508", "kind": "science-record", "revision": 4, "content_hash": "sha256:d8adbe3c51b6fc62139f61c170bb9aee4182b2b5912b2e431856727bc668b900", "created_at": "2026-11-01T19:01:35Z", "updated_at": "2026-11-01T22:51:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of ferroptosis-related hub genes in obstructive sleep apnea syndrome.", "doi": "10.3389/fneur.2023.1130378", "pmid": "36937508", "authors": ["Peijun Liu", "Dong Zhao", "Zhou Pan", "Weihua Tang", "Hao Chen", "Ke Hu"], "journal": "Frontiers in neurology", "year": 2023, "abstract": "Background: By 2020, the prevalence of Obstructive Sleep Apnea Syndrome (OSAS) in the US has reached 26. 6-43.2% in men and 8.7-27.8% in women. OSAS promotes hypertension, diabetes, and tumor growth through unknown means. Chronic intermittent hypoxia (CIH), sleep fragmentation, and increased pleural pressure are central mechanisms of OSAS complications. CIH exacerbates ferroptosis, which is closely related to malignancies. The mechanism of ferroptosis in OSAS disease progression remains unknown.\nMethods: OSAS-related datasets (GSE135917 and GSE38792) were obtained from the GEO. Differentially expressed genes (DEGs) were screened using the R software and intersected with the ferroptosis database (FerrDb V2) to get ferroptosis-related DEGs (f-DEGs). GO, DO, KEGG, and GSEA enrichment were performed, a PPI network was constructed and hub genes were screened. The TCGA database was used to obtain the thyroid cancer (THCA) gene expression profile, and hub genes were analyzed for differential and survival analysis. The mechanism was investigated using GSEA and immune infiltration. The hub genes were validated with RT-qPCR, IHC, and other datasets. Sprague-Dawley rats were randomly separated into normoxia and CIH groups. ROS, MDA, and GSH methods were used to detect CIH-induced ferroptosis and oxidative stress.\nResults: GSEA revealed a statistically significant difference in ferroptosis in OSAS (FDR < 0.05). HIF1A, ATM, HSPA5, MAPK8, MAPK14, TLR4, and CREB1 were identified as hub genes among 3,144 DEGs and 74 f-DEGs. HIF1A and ATM were the only two validated genes. F-DEGs were mainly enriched in THCA. HIF1A overexpression in THCA promotes its development. HIF1A is associated with CD8 T cells and macrophages, which may affect the immunological milieu. The result found CIH increased ROS and MDA while lowering GSH indicating that it could cause ferroptosis. In OSAS patients, non-invasive ventilation did not affect HIF1A and ATM expression. Carvedilol, hydralazine, and caffeine may be important in the treatment of OSAS since they suppress HIF1A and ATM.\nConclusions: Our findings revealed that the genes HIF1A and ATM are highly expressed in OSAS, and can serve as biomarkers and targets for OSAS.", "claims": [{"id": "claim-method", "statement": "We performed a diagnostic curve analysis to assess the significance of hub genes (HIF1A and ATM) in the diagnosis of OSAS. The paired t-test was performed to compare the variation in hub genes expression before and after the application of a non-invasive ventilator. To assess the interaction analysis between hub genes, Pearson correlation analysis was performed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36937508", "locator": "sections[24] \"ROC diagnostic curve and hub genes relationships\" paragraph 2", "quote": "We performed a diagnostic curve analysis to assess the significance of hub genes (HIF1A and ATM) in the diagnosis of OSAS."}, {"asset": "source:pmid:36937508", "locator": "sections[13] \"ROC curve, hub genes relationships, and drug therapy OSAS prediction\" paragraph 2", "quote": "The paired t-test was performed to compare the variation in hub genes expression before and after the application of a non-invasive ventilator."}, {"asset": "source:pmid:36937508", "locator": "sections[24] \"ROC diagnostic curve and hub genes relationships\" paragraph 2", "quote": "To assess the interaction analysis between hub genes, Pearson correlation analysis was performed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36937508", "locator": "sections[28] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The AUC of the combined HIF1A and ATM model for the diagnosis of OSAS was 0.875 in both datasets, suggesting that the model is beneficial for the identification of OSAS (Figures 8C, D).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36937508", "locator": "sections[24] \"ROC diagnostic curve and hub genes relationships\" paragraph 2", "quote": "The AUC of the combined HIF1A and ATM model for the diagnosis of OSAS was 0.875 in both datasets, suggesting that the model is beneficial for the identification of OSAS (Figures 8C, D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The AUC of the combined HIF1A and ATM model for the diagnosis of OSAS was 0.875 in both datasets, suggesting that the model is beneficial for the identification of OSAS (Figures 8C, D).", "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:36937508"], "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:GSE135917"], "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:GSE135917"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36937508", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fneur.2023.1130378", "sha256": "sha256:9fc802864d579b41bf2279a1939d8b4d6f59421d4670b2e9adea96b5578343f1", "bytes": 52608, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fneur.2023.1130378", "version": null, "note": "Full article fetched from PMC; 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The hub genes were validated with RT-qPCR, IHC, and other datasets. Sprague-Dawley rat", "ration. The hub genes were validated with RT-qPCR, IHC, and other datasets. Sprague-Dawley rat"], "order_basis": "paper_text_order:1179", "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": [". The hub genes were validated with RT-qPCR, IHC, and other datasets. Sprague-Dawley rats wer", "proteins in inguinal fat was examined using immunohistochemical techniques in CIH-exposed rats and was signi", "iations in different groups were detected by immunohistochemistry. Magnification × 200, Scare bar, 100 μm. *P", "IH) in rats, validated by ROS, MDA, GSH, and IHC. (A, B) The expression of ROS in rat lung ti"], "order_basis": "paper_text_order:1188", "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": ["PCR, IHC, and other datasets. Sprague-Dawley rats were randomly separated into normoxia and CIH gro", "PCR, IHC, and other datasets. Sprague-Dawley rats were randomly separated into normoxia and CI", "termittent hypoxia group (CIH), in which the mice were kept in a chronic intermittent hypoxic envir", "at Renmin Hospital of Wuhan University. The rats were fed in a 12-h alternating day and night envi"], "order_basis": "paper_text_order:1228", "id": "assay:3"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["We performed a diagnostic curve analysis to assess the significance of hub genes (HIF1A and ATM) in the diagnosis of OSAS. The paired t-test was performed to compare the variation in hub genes expression before and after the application of a non-invasive ventilator. To assess the interaction analysis between hub genes, Pearson correlation analysis was performed."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}