Bioinformatics analyses reveal the autophagy-related feature biomarkers in dilated cardiomyopathy with heart failure.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41614028", "kind": "science-record", "revision": 4, "content_hash": "sha256:a5bd086880d9cebb83f7eeb7be5f2270a6b981433b37d56cae9855faafb6f756", "created_at": "2026-11-01T20:31:43Z", "updated_at": "2026-11-01T22:57:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics analyses reveal the autophagy-related feature biomarkers in dilated cardiomyopathy with heart failure.", "doi": "10.3389/fcvm.2025.1692768", "pmid": "41614028", "authors": ["Jiayu Ren", "Zhihan Li", "Yue Wang", "Ying Wang", "Jing Li"], "journal": "Frontiers in cardiovascular medicine", "year": 2025, "abstract": "Objective: Dilated cardiomyopathy (DCM) is a major cause of heart failure (HF). In this study, we aimed to explore potential autophagy-related biomarkers associated with DCM with HF.\nMethods: The GSE17800 dataset was downloaded from GEO, and differentially expressed genes (DEGs) were identified. Autophagy-related DEGs (AR-DEGs) were obtained by merging DEGs with autophagy-related genes (ARGs) from HADb and HAMdb databases. Gene function enrichment analysis was performed using GO and KEGG. Hub genes were identified via protein-protein interaction (PPI) network analysis, with their expression and diagnostic values validated using the GSE21610 dataset. A doxorubicin (DOX)-induced cardiomyocyte injury model was established to evaluate hub gene expression in vitro and in vivo studies. Potential therapeutic small molecules targeting hub genes were screened via L1000FWD, and their binding affinity to targets was assessed by molecular docking.\nResults: In the GSE17800 dataset, a total of 45 AR-DEGs were identified by intersecting with ARGs from HADb and HAMdb. Through PPI network analysis, 7 hub genes were extracted: CDKN1A, CTSD, DDIT3, EP300, FN1, PKM, and SOD2. Further validation using the GSE21610 dataset showed that receiver operating characteristic (ROC) curve analysis confirmed CTSD and SOD2 had high diagnostic value for DCM with HF. Moreover, in both in vitro and in vivo DOX-induced cardiomyocyte injury models, DOX treatment resulted in upregulated CTSD expression and downregulated SOD2 expression. Additionally, small molecules targeting CTSD and SOD2 (e.g., QL-XII-47 and tipifarnib-P2) were identified as potential therapeutic candidates for DCM with HF.\nConclusion: This study provides novel evidence that CTSD and SOD2 potently contribute to autophagy regulation in DCM with HF. These findings highlight their diagnostic potential for DCM with HF and lay a foundation for exploring targeted small-molecule therapies (e.g., QL-XII-47, tipifarnib-P2) to improve the disease's clinical management.", "claims": [{"id": "claim-method", "statement": "The “limma” package of the R software (version 4.0.1) was used to identify differentially expressed genes (DEGs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41614028", "locator": "sections[5] \"Identification of differentially expressed genes (DEGs) in ARGs\" paragraph 2", "quote": "The “limma” package of the R software (version 4.0.1) was used to identify differentially expressed genes (DEGs)."}], "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:41614028", "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": "In the GSE17800 dataset, a total of 45 AR-DEGs were identified by intersecting with ARGs from HADb and HAMdb.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41614028", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In the GSE17800 dataset, a total of 45 AR-DEGs were identified by intersecting with ARGs from HADb and HAMdb."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In the GSE17800 dataset, a total of 45 AR-DEGs were identified by intersecting with ARGs from HADb and HAMdb.", "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:41614028"], "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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Potential therapeutic small molecul", "DCM with HF. Moreover, in both in vitro and in vivo DOX-induced cardiomyocyte injury models, DOX", "my of Medical Sciences (Beijing, China). All mice were housed under standardized conditions: a 12 h", "cess to standard chow and sterile water. The mice were randomly divided into two groups and receive"], "order_basis": "paper_text_order:847", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": [". Cell culture and treatment AC16 cells were cultured in DMEM/F12 media (10% FBS, 1% penicillin/strep"], "order_basis": "paper_text_order:2968", "id": "assay:2"}, {"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 “limma” package of the R software (version 4.0.1) was used to identify differentially expressed genes (DEGs)."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}