MAPK8 and HDAC6: potential biomarkers related to autophagy in diabetic retinopathy based on bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40469433", "kind": "science-record", "revision": 4, "content_hash": "sha256:77d61338cc0dd96472cad23525f681015db30a5a7c74b2da892a83454cced39c", "created_at": "2026-11-01T20:30:35Z", "updated_at": "2026-11-01T22:56:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "MAPK8 and HDAC6: potential biomarkers related to autophagy in diabetic retinopathy based on bioinformatics analysis.", "doi": "10.3389/fendo.2025.1487007", "pmid": "40469433", "authors": ["Ruotong Sun", "Ling Zuo"], "journal": "Frontiers in endocrinology", "year": 2025, "abstract": "Introduction: One of the most common vascular diseases of the retina is diabetic retinopathy (DR), a microvascular condition caused by diabetes. The autophagy system transports and degrades cytoplasmic substances to lysosomes as part of the intracellular degradation process. Autophagy appears to be an important regulator in the development and progression of DR, but its mechanism and potential role are unclear. The purpose of this study is to identify autophagy-related genes in DR and find potential biomarkers associated with DR through bioinformatics analysis.\nMethod: We retrieved the dataset GSE102485 from the Gene Expression Omnibus (GEO) database and compiled a list of 344 autophagy-related genes. Using the R software, bioinformatics analysis was used to identify the differentially expressed autophagy-related genes (ARGs). Then, we identified the autophagy-related hub genes (ARHGs) through a series of analyses including Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, correlation analysis, and protein-protein interaction (PPI) network. In addition, the miRNA-gene-TF interaction network was generated using the NetworkAnalyst platform. Potential therapeutic drugs were predicted utilizing the Drug-Gene Interaction Database (DGIdb). Ultimately, DR was simulated through the high glucose incubation of the retinal pigment epithelium cell line (ARPE-19), and employing quantitative real-time polymerase chain reaction (qRT-PCR) to verify ARHG expression. The effectiveness of ARHGs in diagnosing DR was assessed by measuring the area under the receiver operating characteristic (ROC) curve.\nResults: Differential expression analysis identified 26 ARGs, of which 6 were upregulated and 20 were downregulated. Through GO and KEGG enrichment analysis, it was found that ARGs showed significant enrichment in autophagy-related pathways. Using PPI network analysis, 7 ARHGs were identified. The expression of MAPK8, HDAC6, DNAJB1 and TARDBP, in a model of DR were confirmed by qRT-PCR. The ROC curve results showed that MAPK8, HDAC6, DNAJB1 and TSC2 had high predictive accuracy and could be used as biomarkers for DR.\nConclusion: Through bioinformatics analysis, we identified 26 genes that may be associated with autophagy in DR. We suggest that the hub genes MAPK8 and HDAC6 as biomarkers may be involved in autophagy in DR.", "claims": [{"id": "claim-method", "statement": "The “limma” package (16) was used to screen for differential genes between the control and DR groups. We considered genes with adjusted p-values <0.05 and |log fold change|>1 as differentially expressed genes. The analysis of gene expression levels within the sample was conducted employing the Student’s t-test, and the observed difference was deemed to be statistically significant when P <0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40469433", "locator": "sections[4] \"Differential expression analysis\" paragraph 2", "quote": "The “limma” package (16) was used to screen for differential genes between the control and DR groups."}, {"asset": "source:pmid:40469433", "locator": "sections[4] \"Differential expression analysis\" paragraph 2", "quote": "We considered genes with adjusted p-values <0.05 and |log fold change|>1 as differentially expressed genes."}, {"asset": "source:pmid:40469433", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "The analysis of gene expression levels within the sample was conducted employing the Student’s t-test, and the observed difference was deemed to be statistically significant when P <0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: http://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40469433", "locator": "sections[25] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: http://www.ncbi.nlm.nih.gov/geo/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Then, 26 ARGs in DR were obtained, including 6 upregulated genes and 20 downregulated genes ( Table 1 ).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40469433", "locator": "sections[14] \"Identification of differentially expressed ARGs\" paragraph 2", "quote": "Then, 26 ARGs in DR were obtained, including 6 upregulated genes and 20 downregulated genes ( Table 1 )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Then, 26 ARGs in DR were obtained, including 6 upregulated genes and 20 downregulated genes ( Table 1 ).", "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:40469433"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE102485"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE102485"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40469433", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2025.1487007", "sha256": "sha256:c6c11f84933d1e7d458ab4a183c793b4ecb2c3b1163a90b8f2146b531650ae97", "bytes": 59119, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2025.1487007", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12133481", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE102485", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102485", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE102485", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: http://www.ncbi.nlm.nih.gov/geo/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: http://www.ncbi.nlm.nih.gov/geo/.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2739339", "GSM2739340", "GSM2739341", "GSM2739342", "GSM2739343", "GSM2739344", "GSM2739345", "GSM2739346", "GSM2739347", "GSM2739348", "GSM2739349", "GSM2739350", "GSM2739351", "GSM2739352", "GSM2739353", "GSM2739354", "GSM2739355", "GSM2739356", "GSM2739357", "GSM2739358", "GSM2739359", "GSM2739360", "GSM2739361", "GSM2739362", "GSM2739363", "GSM2739364", "GSM2739365", "GSM2739366", "GSM2739367", "GSM2739368"], "sample_count": 30, "group_sizes": null, "group_sizes_basis": null, "platform": "18573", "taxon": "Homo sapiens", "title": "Induced Expression of VEGFC, ANGPT, and EFNB2 and Their Receptors Characterizes Neovascularization in Proliferative Diabetic Retinopathy", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE221521", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE221521", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE221521", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: http://www.ncbi.nlm.nih.gov/geo/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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