The mitochondrial hub gene UCHL1 May serve as a potential biomarker for diagnosing diabetic cardiomyopathy: a comprehensive integration of biological pathways.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40790764", "kind": "science-record", "revision": 4, "content_hash": "sha256:ee88606212433524e72f11280f07a462f0f5cae5e6befb564b6c496267e17712", "created_at": "2026-11-01T20:30:53Z", "updated_at": "2026-11-01T22:56:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The mitochondrial hub gene UCHL1 May serve as a potential biomarker for diagnosing diabetic cardiomyopathy: a comprehensive integration of biological pathways.", "doi": "10.1186/s12920-025-02199-0", "pmid": "40790764", "authors": ["Chengjie Gao", "Yijing Tao", "Da Qian", "Yafeng Zhou"], "journal": "BMC medical genomics", "year": 2025, "abstract": "BACKGROUND: Diabetic cardiomyopathy (DCM) is a complex clinical syndrome characterized by cardiac systolic and diastolic dysfunction. Research on the underlying mechanism of mitochondrial dysfunction and the involved genes in patients with DCM is limited.\nOBJECTIVE: We aimed to explore the hub genes and pathways related to mitochondrial dysfunction that affect the progression of DCM.\nMETHODS: DCM patient datasets (GSE161052, GSE210611 (test sets) and GSE26887 (validation set) were downloaded from the Gene Expression Omnibus (GEO) database. The identification of the differentially expressed genes (DEGs) was performed using the \"limma\" R package. Mitochondrial dysfunction-related genes (MDRGs) associated with DCM were obtained from the Molecular Signatures Database (MSigDB). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to analyse the biological function of mitochondrial dysfunction-related differentially expressed genes (MDRDEGs) via the \"ClusterProfiler\", \"DOSE\", \"org.Hs.eg.db\" and \"circlize\" R packages. The diagnostic value of the hub genes for DCM was confirmed using receiver operating characteristic (ROC) curves in the test and validation groups. Moreover, the functions of the hub genes in the context of DCM were explored via gene set enrichment analysis (GSEA). A protein‒protein interaction (PPI) network of the hub genes was constructed using the GeneMANIA database. Finally, real-time reverse transcription polymerase chain reaction (real-time RT PCR) analysis and western blot analysis were performed to detect the expression levels of UCHL1.\nRESULTS: A total of 705 DEGs and 122 MDRGs closely related to DCM were identified, and 6 MDRDEGs (AGT, KIT, SLC2A1, SLC2A4, TK2, and UCHL1) were obtained and subjected to GO and KEGG enrichment analyses. ROC curve analysis was performed for the test and validation groups. Only the AUC of UCHL1 reached 1.0 in both the test and validation groups, and UCHL1 was identified as a hub gene in DCM. GSEA revealed that multiple biological pathways were activated or inhibited along with alterations in the expression of UCHL1. PPI network analysis revealed that the hub genes interacted with mainly the ASPSCR1, PTPRU, STXBP3, SOCS6 and UCHL5 proteins. There was a reciprocal regulatory relationship between UCHL1 expression and hsa-miR-181a-5p, hsa-miR-193b-3p, hsa-miR-877-5p and hsa-miR-218-5p levels. Finally, real-time RT PCR and western blot analysis revealed that UCHL1 may be used as a potential diagnostic biomarker of DCM.\nCONCLUSIONS: In this study, 6 mitochondrial dysfunction-related hub genes related to DCM were identified. The mitochondrial hub gene UCHL1 was demonstrated to be a potential diagnostic biomarker for DCM.", "claims": [{"id": "claim-method", "statement": "The identification of DEGs between DCM tissue samples and normal tissue samples was performed by using the “limma” R package [14].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40790764", "locator": "sections[4] \"Identification of differentially expressed genes\" paragraph 2", "quote": "The identification of DEGs between DCM tissue samples and normal tissue samples was performed by using the “limma” R package [14]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analysed in this study. These data can be found in the GEO database (http://www.ncbi.nlm.nih.gov/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40790764", "locator": "sections[27] \"Data availability\" paragraph 2", "quote": "Publicly available datasets were analysed in this study. These data can be found in the GEO database (http://www.ncbi.nlm.nih.gov/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 705 DEGs and 122 MDRGs closely related to DCM were identified, and 6 MDRDEGs (AGT, KIT, SLC2A1, SLC2A4, TK2, and UCHL1) were obtained and subjected to GO and KEGG enrichment analyses.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40790764", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "A total of 705 DEGs and 122 MDRGs closely related to DCM were identified, and 6 MDRDEGs (AGT, KIT, SLC2A1, SLC2A4, TK2, and UCHL1) were obtained and subjected to GO and KEGG enrichment analyses."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 705 DEGs and 122 MDRGs closely related to DCM were identified, and 6 MDRDEGs (AGT, KIT, SLC2A1, SLC2A4, TK2, and UCHL1) were obtained and subjected to GO and KEGG enrichment analyses.", "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:40790764"], "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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Finally, real-time RT PCR and western blot analysis revealed that UCHL1 may be used as", "transcription polymerase chain reaction and western blot analysis of the hub genes The heart was fixe"], "order_basis": "paper_text_order:1665", "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": ["Materials and methods Histological analysis, immunohistochemistry analysis, real-time reverse transcription po", "ining using the standard procedure [22, 23]. Immunohistochemical staining was performed as described previous"], "order_basis": "paper_text_order:2920", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["T PCR) was conducted with RealStar Fast SYBR Qpcr Mix (GenStar, #A304). Primers for this study"], "order_basis": "paper_text_order:3891", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["is study are as follows: GeneSequence (5’-3’)Mouse-β-actin-ForwardGTGACGTTGACATCCGTAAAGAMouse-β"], "order_basis": "paper_text_order:3977", "id": "assay:4"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The identification of DEGs between DCM tissue samples and normal tissue samples was performed by using the “limma” R package [14]."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}