Identification of Optic Nerve-Related Biomarkers in Primary Open-Angle Glaucoma Based on Comprehensive Bioinformatics and Mendelian Randomization.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39133496", "kind": "science-record", "revision": 2, "content_hash": "sha256:83770157aa6af1264cfa4b98027fb07286d8c947606b43cf16b3abb9e26e101c", "created_at": "2026-11-01T20:29:14Z", "updated_at": "2026-11-01T21:33:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Optic Nerve-Related Biomarkers in Primary Open-Angle Glaucoma Based on Comprehensive Bioinformatics and Mendelian Randomization.", "doi": "10.1167/tvst.13.8.21", "pmid": "39133496", "authors": ["Sijie Zhao", "Qing Dai", "Zixuan Rao", "Juan Li", "Aiqin Wang", "Ziqing Gao", "Yuchen Fan"], "journal": "Translational vision science & technology", "year": 2024, "abstract": "Purpose: Glaucoma is the primary cause of permanent vision loss worldwide. However, the pathogenesis of primary open-angle glaucoma (POAG), the main type of glaucoma, has not yet been completely understood.\nMethods: In our study, the POAG cohorts were obtained from the Gene Expression Omnibus (GEO) database (GSE45570). Biomarkers with diagnostic utility for POAG were identified through combining differentially expressed analysis, enrichment analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. The regulatory networks (including a competing endogenous RNA (ceRNA) regulatory network and a small molecule compounds-mRNA network) were created. In addition, the Mendelian randomization (MR) analysis was used to identify exposures causally associated with POAG. Finally, the expression of the biomarkers was validated via real-time quantitative polymerase chain reaction (RT-qPCR).\nResults: The Gene Ontology (GO) items that the differentially expressed genes (DEGs) between POAG and control groups enriched were relevant to light stimulation and DNA methylation. A total of three light stimulation-related biomarkers (RAB8A, PRG3, and SMAD3) were identified, which had diagnostic value for POAG patients. Besides, the ceRNA regulatory network contained 88 nodes and 93 edges, and a small molecule compounds-mRNA network included 66 nodes and 76 edges. The MR results indicated a causal association between DNA methylation GrimAge acceleration and POAG. Additionally, the results of RT-qPCR revealed that the expression trend of RAB8A was consistent with that of GSE45570.\nConclusions: Taken together, this study provides three light stimulation-related biomarkers (RAB8A, PRG3, and SMAD3) for the diagnosis of POAG, providing scientifically valuable insights for further studies of POAG.\nTranslational Relevance: Discovering biomarkers that possess diagnostic significance for POAG has the potential to offer new insights into the pathogenesis of POAG and present novel objectives for clinical intervention.", "claims": [{"id": "claim-method", "statement": "MR analysis was carried out via five methods: weighted median, MR–Egger, simple mode, inverse variance weighted (IVW), and weighted mode.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39133496", "locator": "sections[6] \"MR Analysis\" paragraph 3", "quote": "MR analysis was carried out via five methods: weighted median, MR–Egger, simple mode, inverse variance weighted (IVW), and weighted mode."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE45570—[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]—was acquired from the GEO database (https://ww.ncbinlm.nih.gov/), containing six ONH samples from patients with POAG and six normal ONH samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39133496", "locator": "sections[3] \"Microarray Data Acquisition\" paragraph 2", "quote": "The GSE45570—[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]—was acquired from the GEO database (https://ww.ncbinlm.nih.gov/), containing six ONH samples from patients with POAG and six normal ONH samples."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of three light stimulation-related biomarkers (RAB8A, PRG3, and SMAD3) were identified, which had diagnostic value for POAG patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39133496", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of three light stimulation-related biomarkers (RAB8A, PRG3, and SMAD3) were identified, which had diagnostic value for POAG patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of three light stimulation-related biomarkers (RAB8A, PRG3, and SMAD3) were identified, which had diagnostic value for POAG patients.", "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:39133496"], "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:GSE45570"], "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:GSE45570"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39133496", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1167/tvst.13.8.21", "sha256": "sha256:0821513664808b81c1e339dc17ddeeb35e3113030f290ae5dcf0091cd03b9e98", "bytes": 35151, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1167/tvst.13.8.21", "version": null, "note": "Full article fetched from PMC; 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