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pmid:41079183
Shared senescence-associated gene networks in PCOS and T2DM: biomarker identification and functional validation.
Mingyue Kong · Kun Lou · Dan Liu · Ziqi Dai · Tianjiao Li · Yihan Yang · Xuesong Zhang · Xin Chen
Frontiers in endocrinology · 2025 doi:10.3389/fendo.2025.1652178
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Experiment
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Complete file
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Cellular senescence may represent a pivotal process driving the progression of both conditions. Senescent cells, through the senescence-associated secretory phenotype (SASP), can induce chronic inflammation, which is highly likely to exacerbate the pathological progression of PCOS and T2DM. However, the molecular pathways linking cellular senescence to PCOS and T2DM have not yet been systematically elucidated.\nMethods: The transcriptome datasets of PCOS (GSE54248) and T2DM (GSE23561) were obtained from the GEO database, and differentially expressed genes (DEGs) were screened using the limma package. Age-related DEGs (ARDEGs) were obtained by intersecting DEGs with age-related genes, and the protein-protein interaction (PPI) network was constructed based on the STRING database. Hub genes with diagnostic value were determined via the Wilcoxon rank sum test and receiver operating characteristic (ROC) curve. CIBERSORT was used to analyze the infiltration characteristics of immune cells, and the functions of the hub gene were analyzed by gene set enrichment analysis (GSEA). Single-cell sequencing was used to locate gene expression patterns, and qRT-PCR was used to verify the expression of candidate genes in clinical samples.\nResults: 80 DEGs between PCOS and T2DM samples were obtained, and 15 ARDEGs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that they were related to inflammatory response and immune response, and were involved in specific functions and pathways. Four hub genes were identified: TUBA4A, RTN1, G6PD, and HP. qRT-PCR experimental results showed that HP, G6PD, TUBA4A, and RTN1 were highly expressed in the peripheral blood of PCOS and T2DM patients, compared to healthy people.\nDiscussion: This study revealed the potential connections between PCOS, T2DM, and aging-related molecular networks and signaling pathways and discovered multiple potential therapeutic targets. It provides new intervention directions for clinicians, especially based on aging mechanisms.", "claims": [{"id": "claim-method", "statement": "DEGs from each dataset were found via the R package “limma,”with the criteria set as p < 0.05 and |logFC| > 0.585. 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Variance between samples was corrected using empirical Bayes moderation (eBayes function)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41079183", "locator": "sections[27] \"Data availability statement\" paragraph 2", "quote": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 80 shared DEGs, 15 age-related DEGs, and four diagnostic hub genes: TUBA4A, RTN1, G6PD, and HP.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41079183", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "80 DEGs between PCOS and T2DM samples were obtained, and 15 ARDEGs were identified."}, {"asset": "source:pmid:41079183", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Four hub genes were identified: TUBA4A, RTN1, G6PD, and HP."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study identified 80 shared DEGs, 15 age-related DEGs, and four diagnostic hub genes: TUBA4A, RTN1, G6PD, and HP.", "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:41079183"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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