Identification of the cuproptosis-related hub genes and therapeutic agents for sarcopenia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37007946", "kind": "science-record", "revision": 3, "content_hash": "sha256:6e1abb5eebb6c55d5ea3193a47efaf8d3b34fdf09f4783d753b852e1fd69add0", "created_at": "2026-11-01T19:01:40Z", "updated_at": "2026-11-01T22:09:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of the cuproptosis-related hub genes and therapeutic agents for sarcopenia.", "doi": "10.3389/fgene.2023.1136763", "pmid": "37007946", "authors": ["Yingqian Zhu", "Xin Chen", "Shasha Geng", "Qingqing Li", "Yang Li", "Huixiao Yuan", "Hua Jiang"], "journal": "Frontiers in genetics", "year": 2023, "abstract": "Background: Along with acceleration of population aging, the increasing prevalence of sarcopenia has posed a heavy burden on families as well as society. In this context, it is of great significance to diagnose and intervene sarcopenia as early as possible. Recent evidence has indicated the role of cuproptosis in the development of sarcopenia. In this study, we aimed to seek the key cuproptosis-related genes that can be used for identification and intervention of sarcopenia. Methods: The GSE111016 dataset was retrieved from GEO. The 31 cuproptosis-related genes (CRGs) were obtained from previous published studies. The differentially expressed genes (DEGs) and Weighed gene co-expression network analysis (WGCNA) were subsequently analyzed. The core hub genes were acquired by the intersection of DEGs, WGCNA and CRGs. Through logistic regression analysis, we established a diagnostic model of sarcopenia based on the selected biomarkers and was validated in muscle samples from GSE111006 and GSE167186. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were performed on these genes. Furthermore, the gene set enrichment analysis (GSEA), and immune cell infiltration were also conducted on the identified core genes. Finally, we screened the potential drugs targeting the potential biomarkers of sarcopenia. Results: A total of 902 DEGs and WGCNA containing 1,281 significant genes were preliminarily selected. Intersection of DEGs, WGCNA and CRGs yielded four core genes (PDHA1, DLAT, PDHB, and NDUFC1) as potential biomarkers for the prediction of sarcopenia. The predictive model was established and validated with high AUC values. KEGG pathway and Gene Ontology biological analysis indicated these core genes may play a crucial role in energy metabolism in mitochondria, oxidation process, and aging-related degenerative diseases. In addition, the immune cells may be involved in the development of sarcopenia through mitochondrial metabolism. Finally, metformin was identified as a promising strategy of sarcopenia treatment via targeting NDUFC1. Conclusion: The four cuproptosis-related genes PDHA1, DLAT, PDHB and NDUFC1 may be the diagnostic biomarkers for sarcopenia, and metformin holds great potential to be developed as a therapy for sarcopenia. These outcomes provide new insights for better understanding of sarcopenia and innovative therapeutic approaches.", "claims": [{"id": "claim-method", "statement": "Then, the ROC curve analysis of multigene prediction model of sarcopenia was constructed via logistic regression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37007946", "locator": "sections[15] \"Construction and verification of multigene diagnostic model\" paragraph 2", "quote": "Then, the ROC curve analysis of multigene prediction model of sarcopenia was constructed via logistic regression."}], "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:37007946", "locator": "sections[22] \"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 four-gene diagnostic model for sarcopenia achieved an AUC of 0.83 in the training dataset and was validated with AUC values of 0.87 in GSE111006 and 0.64 in GSE167186.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37007946", "locator": "sections[15] \"Construction and verification of multigene diagnostic model\" paragraph 2", "quote": "To evaluate the sensitivity and specificity for the prediction model, the area under the curve (AUC) values of the four hub genes were calculated with the value of 0.83, which indicated the high predictive value of the hub genes for sarcopenia (Figure 5B)."}, {"asset": "source:pmid:37007946", "locator": "sections[15] \"Construction and verification of multigene diagnostic model\" paragraph 2", "quote": "To further confirm the utility of this model, the diagnostic value of the four hub genes was validated in two independent datasets subsequently, with AUC values of 0.87 in GSE111006 dataset and 0.64 in GSE167186 dataset (Figures 5C,D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The four-gene diagnostic model for sarcopenia achieved an AUC of 0.83 in the training dataset and was validated with AUC values of 0.87 in GSE111006 and 0.64 in GSE167186.", "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:37007946"], "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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