Multiple Hub Genes as Diagnostic and Therapeutic Targets Inducing Inflammation and Angiogenesis in Retinopathy of Prematurity.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40786954", "kind": "science-record", "revision": 4, "content_hash": "sha256:dfe13993b9532592ef9a3a127c3ccfa11e26f0b18a06f5de4232f6e8f6b63b6c", "created_at": "2026-11-01T20:30:52Z", "updated_at": "2026-11-01T22:56:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Multiple Hub Genes as Diagnostic and Therapeutic Targets Inducing Inflammation and Angiogenesis in Retinopathy of Prematurity.", "doi": "10.2147/IJGM.S528842", "pmid": "40786954", "authors": ["Cheng Du", "Yuan Tian", "Yu Liu", "Yuanyuan Shi", "Xingying Chen", "Hui Chai", "Yuyan Zhang", "Hui Shen", "Lin Zhang"], "journal": "International journal of general medicine", "year": 2025, "abstract": "Introduction: The pathogenesis of retinopathy of prematurity (ROP) is intricate and multifactorial. The current treatments for ROP include laser photocoagulation, cryotherapy, scleral buckling or vitrectomy and anti-VEGF drugs, yet which have numerous adverse effects. Consequently, the objective of this investigation was to mine new biomarkers of ROP and identify potential therapeutics that target these biomarkers.\nMethods: GSE130400, the expression profile of ROP, was downloaded from the GEO database and annotated by dplyr package in R. The limma package was employed to identify differentially expressed genes (DEGs) between cases and controls. WGCNA was utilized to obtain oxygen-induced retinopathy (OIR)-related modules, and then key genes were obtained in the intersection of DEGs and the above modules. Biological functions and pathways of key genes were enriched through DAVID, Metascape and Gene set enrichment analysis. Hub genes were screened by three machine learning methods and validated by nomograms, ROC curves and qRT-PCR. CIBERSORT was used to estimate the abundances of immune cells and Pearson analysis revealed immune cells, checkpoints and chemokines associated with hub genes. Finally, we constructed a ceRNA network and a drug-gene interaction network.\nResults: Utilizing GSE130400 as a basis, a total of 798 DEGs and 3711 genes from three OIR-related modules in WGCNA were identified, resulting in the identification of 681 key genes. Hub genes Plxnd1, Esm1 and Cd248 were explored using various machine learning methods and proved to be closely related with the occurrence of ROP through nomograms, ROC curves and qRT-PCR. Enrichment analysis revealed a significant enrichment of hub genes in processes related to endothelial cell proliferation, migration, and angiogenesis, among others. Immune analysis displayed that the development of ROP was associated with alterations in M0 macrophages and M2 macrophages, with hub genes participating in the regulation of immune cells M0 macrophages, Th2 cells, and NK resting cells, as well as chemokines lncRNA H19 (H19), CXCR5 (F5), CCL27 (F7) and CCL2 (C2). Furthermore, the drug-gene interaction network displayed 14 possible candidate drugs targeting 3 hub genes.\nConclusion: Plxnd1, Esm1 and Cd248 might play significant roles in the progression of ROP and could become possible diagnostic and therapeutic targets in ROP.", "claims": [{"id": "claim-method", "statement": "Differentially expressed analysis (|log2FC| ≥ 1, adjusted p-value < 0.05) was conducted via comparing oxygen-induced retinopathy (OIR) tissues to normal tissues in the R computing environment employing the Linear Model Fitting (LimFit) package and the Empirical Bayes (eBayes) of the limma package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40786954", "locator": "sections[4] \"Differentially Expressed Analysis\" paragraph 2", "quote": "Differentially expressed analysis (|log2FC| ≥ 1, adjusted p-value < 0.05) was conducted via comparing oxygen-induced retinopathy (OIR) tissues to normal tissues in the R computing environment employing the Linear Model Fitting (LimFit) package and the Empirical Bayes (eBayes) of the limma package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130400.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40786954", "locator": "sections[27] \"Data Sharing Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130400."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 798 DEGs, including 190 down-regulated and 608 up-regulated genes, were identified between OIR and control samples and displayed in the volcano plot (Figure 2A).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40786954", "locator": "sections[15] \"Identification of DEGs Potentially Associated with ROP\" paragraph 2", "quote": "A total of 798 DEGs, including 190 down-regulated and 608 up-regulated genes, were identified between OIR and control samples and displayed in the volcano plot (Figure 2A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 798 DEGs, including 190 down-regulated and 608 up-regulated genes, were identified between OIR and control samples and displayed in the volcano plot (Figure 2A).", "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:40786954"], "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:GSE130400"], "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:GSE130400"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40786954", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S528842", "sha256": "sha256:97653df5600307e6e01928726adcca48b921a15ebad32fa1fc7e44a8308fc5bb", "bytes": 63793, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/IJGM.S528842", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12335267", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE130400", "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=GSE130400", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE130400", "version": null, "note": "Publicly available datasets were analyzed in this study. 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