Identification and validation of key mitophagy-related biomarkers in the pathogenesis of proliferative diabetic retinopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41234227", "kind": "science-record", "revision": 3, "content_hash": "sha256:59415164e06e061376ddf8a3d788188a0041126e08b9a70ca6d7046f74ceec8d", "created_at": "2026-11-01T20:31:16Z", "updated_at": "2026-11-01T22:15:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of key mitophagy-related biomarkers in the pathogenesis of proliferative diabetic retinopathy.", "doi": "10.3389/fendo.2025.1652898", "pmid": "41234227", "authors": ["Yifan Liu", "Ye Zhou", "Jie Chen", "Jiahui Jin", "Xueying Wang", "Xi Wang", "Jieping Zhang", "Jiao Li", "Junfang Zhang", "Ling Zhu", "Guo-Tong Xu", "Yanlong Bi", "Qingjian Ou", "Caixia Jin"], "journal": "Frontiers in endocrinology", "year": 2025, "abstract": "Introduction: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus, and proliferative diabetic retinopathy (PDR) represents its advanced stage. The etiology of PDR is complex. Mitophagy, the selective degradation of dysfunctional mitochondria, is crucial for cellular homeostasis and has been implicated in PDR pathogenesis. However, its specific mechanisms require further investigation.\nMaterials and methods: Gene Expression Omnibu (GEO) datasets (GSE102485, GSE60436) were analyzed in R software to identify differentially expressed mitophagy-related genes (DEMRGs). A PDR diagnostic model was constructed by gene ontology (GO) enrichment analysis, genome enrichment analysis (GSEA), and other relevant methods. Immune infiltration was also performed to analyze the changes in immune cells. Finally, the retinal pigment epithelial cell line (ARPE-19) was incubated with high glucose (HG) to simulate a DR model in vitro, hub-gene expression and mitophagy were assessed by qRT-PCR, Western blotting, and immunofluorescence microscopy (IF).\nResults: Eight DEMRGs were identified enabling construction of a PDR diagnostic model and prioritization of two hub genes (CASP8 and COL1A1). Finally, qRT-PCR, Western blotting, and IF were performed to provide preliminary validation of the PDR model and HG stimulation increased mitochondria-lysosome colocalization as well as enhanced the expression of mitophagy-related proteins.\nConclusion: Integrated bioinformatics and experimental validation suggest that mitophagy contributes to PDR pathogenesis. Five DEMRGs showed up-regulated and immune cell infiltration that may affect the occurrence and PDR development by regulating mitophagy. These findings provide candidate biomarkers and mechanistic insight into PDR.", "claims": [{"id": "claim-method", "statement": "Least Absolute Shrinkage and Selection Operator (LASSO) regression is a technique employed to reduce the dimensionality of data.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41234227", "locator": "sections[7] \"Constructing diagnostic models\" paragraph 2", "quote": "Least Absolute Shrinkage and Selection Operator (LASSO) regression is a technique employed to reduce the dimensionality of data."}], "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/s.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41234227", "locator": "sections[27] \"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/s."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In the Validation dataset, the AUC was recorded at 0.833 ( Figure 4C ), further confirming the model’s efficacy in generalizing its predictive capabilities beyond the training data.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41234227", "locator": "sections[21] \"Constructing a diagnostic model for PDR\" paragraph 2", "quote": "In the Validation dataset, the AUC was recorded at 0.833 ( Figure 4C ), further confirming the model’s efficacy in generalizing its predictive capabilities beyond the training data."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "In the Validation dataset, the AUC was recorded at 0.833 ( Figure 4C ), further confirming the model’s efficacy in generalizing its predictive capabilities beyond the training data.", "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:41234227"], "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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Res", "genes (CASP8 and COL1A1). Finally, qRT-PCR, Western blotting, and IF were performed to provide preliminar"], "order_basis": "paper_text_order:1113", "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": 0.93, "evidence": ["e assessed by qRT-PCR, Western blotting, and immunofluorescence microscopy (IF). Results: Eight DEMRGs were"], "order_basis": "paper_text_order:1135", "id": "assay:2"}, {"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": ["normal control (NC) group. The HG group was cultured in medium containing 30 mmol/L D-glucose, while", "30 mmol/L D-glucose, while the NC group was cultured in standard glucose (SG) medium. A volume of 2."], "order_basis": "paper_text_order:2563", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}