Comprehensive analysis of cuproptosis-related genes in diabetic cardiomyopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41144543", "kind": "science-record", "revision": 3, "content_hash": "sha256:f6615e23d2c903862338a35511bb3f6d7696bc49194748021deb44db70eb9d5e", "created_at": "2026-11-01T20:31:11Z", "updated_at": "2026-11-01T22:14:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of cuproptosis-related genes in diabetic cardiomyopathy.", "doi": "10.1371/journal.pone.0328512", "pmid": "41144543", "authors": ["Jun Li", "Hua Zhang", "Xinyue Duan", "Meina Zhang", "Xin Li", "Chunyan Hao"], "journal": "PloS one", "year": 2025, "abstract": "BACKGROUND: Diabetic cardiomyopathy (DCM) represents a distinct myocardial pathology arising from chronic diabetic metabolic disturbances, characterized by progressive structural and functional abnormalities that frequently culminate in heart failure. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, studies are limited on the clinical significance of cuproptosis-related genes (CRGs) in DCM. Therefore, it is helpful to identify CRGs involved in DCM and explore their expression and molecular mechanisms.\nMETHODS: We downloaded three datasets of DCM from the GEO database and a set of cuproptosis-related genes with 176 genes. Following the identification of the differentially expressed cuproptosis-related genes(DECRGs) and hub genes, we performed the functional annotation, protein-protein interaction network, co-expression network analysis, mRNA-miRNA regulatory network.The GSE5606 dataset was then used to verify hub genes. Finally, we validated the expression of hub genes in a high glucose-induced H9C2 cell injury model via RT-qPCR.\nRESULTS: We identified 14 DEFRGs and 7 key genes in the DCM samples compared to the control. Functional enrichment analysis revealed that DECRGs are associated with several pathways, including TCA cycle, respiratory electron transport, oxidative stress, and metabolism pathway. Moreover, Isocitrate dehydrogenase 1(Idh1), Cytochrome P450 Family 1 Subfamily A Member 1(Cyp1a1), 3-Hydroxy-3-Methylglutaryl-CoA Synthase (Hmgcs2) and Hexokinase 2(Hk2) were identified as the hub genes and validated in the GSE5606 datasets with area under the curve(AUC)>0.7. The qRT-PCR results showed that the expression levels of Cyp1a1, Hmgcs2, HK2, and Idh1 in vitro model of DCM and controls were consistent with the bioinformatics analysis results from the mRNA microarray.\nCONCLUSIONS: Overall,we identified hub genes and pathways involved in DCM via bioinformatics analysis and revealed the potential role of cuproptosis, providing useful and novel information to explore the potential candidate genes for DCM diagnostic and therapeutic options.", "claims": [{"id": "claim-method", "statement": "The expression data of 7 hub genes were extracted, and groups were compared using the Student’s t-test. To evaluate the diagnostic performance of 7 hub genes, the ROC was plotted using the“pROC”R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41144543", "locator": "sections[10] \"Validation of hub genes in GSE5606\" paragraph 2", "quote": "The expression data of 7 hub genes were extracted, and groups were compared using the Student’s t-test. To evaluate the diagnostic performance of 7 hub genes, the ROC was plotted using the“pROC”R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the manuscript and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41144543", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the manuscript and its Supporting Information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 14 differentially expressed cuproptosis-related genes and 7 hub genes, with Idh1, Cyp1a1, Hmgcs2, and Hk2 showing AUC values greater than 0.7 in the GSE5606 validation dataset.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41144543", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified 14 DEFRGs and 7 key genes in the DCM samples compared to the control."}, {"asset": "source:pmid:41144543", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Moreover, Isocitrate dehydrogenase 1(Idh1), Cytochrome P450 Family 1 Subfamily A Member 1(Cyp1a1), 3-Hydroxy-3-Methylglutaryl-CoA Synthase (Hmgcs2) and Hexokinase 2(Hk2) were identified as the hub genes and validated in the GSE5606 datasets with area under the curve(AUC)>0.7."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 14 differentially expressed cuproptosis-related genes and 7 hub genes, with Idh1, Cyp1a1, Hmgcs2, and Hk2 showing AUC values greater than 0.7 in the GSE5606 validation dataset.", "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:41144543"], "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. 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RESULTS: We identified 14 DEFRGs and 7 key", "lucose-induced H9C2 cell injury model via RT-qPCR. RESULTS: We identified 14 DEFRGs and 7 key"], "order_basis": "paper_text_order:1154", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ioinformatics analysis results from the mRNA microarray. CONCLUSIONS: Overall,we identified hub gene"], "order_basis": "paper_text_order:1911", "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": 0.642, "evidence": ["and establishment of vitro model of DCM H9C2 rat cardiomyocytes were purchased from Wuhan Pri"], "order_basis": "paper_text_order:2282", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ella Biotechnology Co., Ltd. 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