Identification of potential biomarkers and therapeutic targets for underactive bladder based on bioinformatics analysis and experimental validation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41196851", "kind": "science-record", "revision": 4, "content_hash": "sha256:51a5acc75013c347fa78670a3b3e2d65285c5710726931db0186346de8b2985d", "created_at": "2026-11-01T20:31:14Z", "updated_at": "2026-11-01T22:57:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of potential biomarkers and therapeutic targets for underactive bladder based on bioinformatics analysis and experimental validation.", "doi": "10.1371/journal.pone.0335455", "pmid": "41196851", "authors": ["Chen Chen", "Zhuojing Hu", "Yunbo Ma", "Qinghua Xia", "Zheng Ma", "Jiangsong Li", "Wei Zhao"], "journal": "PloS one", "year": 2025, "abstract": "Underactive bladder (UAB) is a common disorder that significantly affects patients' quality of life, necessitating the exploration of underlying molecular mechanisms for more effective management. This study aims to elucidate the gene expression profiles associated with UAB by employing a combination of bioinformatics analyses and experimental validation to identify pivotal hub genes and potential therapeutic targets. We accessed the GSE122060 and GSE100219 datasets from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs), followed by functional enrichment analysis, construction of a protein-protein interaction (PPI) network, screening for hub genes and assess the accuracy and diagnostic value of the hub genes with the validation dataset GSE28242. Eighty-five DEGs were identified from the GEO dataset, with functional enrichment analysis focusing primarily on biological processes like neutrophil migration, cell chemotaxis, and bacterial defense responses. Twelve key genes were identified in the PPI network using CytoHubba and MCODE plugins. Of these, C3, CLEC4E, CSF3R, CXCR2, FPR2, and IDO1 showed significant upregulation in the validation set compared to the control group. Receiver operating characteristic (ROC) curve analysis demonstrated that these six hub genes possess high diagnostic potential, with area under the curve (AUC) values greater than 0.76. Additionally, a hub gene-transcription factor (TF) interaction network, a hub gene-TF-miRNA co-regulatory network and a hub gene-drug interaction network were constructed, revealing that five TFs and five miRNAs regulate three or more hub genes. Quantitative real-time polymerase chain reaction (qRT-PCR) validation confirmed the differential expression patterns of the 12 key genes in the PPI network in TGF-β1 treated SV-HUC-1 cells. In conclusion, our findings suggest that CLEC4E, CSF3R, CXCR2, FPR2, and IDO1 can serve as promising diagnostic biomarkers for UAB, while the identified TFs and miRNAs could unveil new avenues for drug discovery and therapeutic interventions targeting UAB progression.", "claims": [{"id": "claim-method", "statement": "We used the GEO2R tool to analyze, standardize, and clean the data according to the sample sequencing platform. The threshold for DEGs is set at |log2 fold change (FC)| > 1 and p.adj (Benjamini & Hochberg) < 0.05. All statistical evaluations were conducted utilizing R software (version 4.2.1) in conjunction with GraphPad Prism 9 software. The determination of statistical significance for differences between groups and among multiple groups was carried out through the application of the t-test and one-way analysis of variance (ANOVA), respectively. Perform diagnostic receiver operating characteristic (ROC) curve analysis with the pROC package and visualize the results using ggplot2.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41196851", "locator": "sections[3] \"Data acquisition and analysis\" paragraph 2", "quote": "We used the GEO2R tool to analyze, standardize, and clean the data according to the sample sequencing platform."}, {"asset": "source:pmid:41196851", "locator": "sections[3] \"Data acquisition and analysis\" paragraph 2", "quote": "The threshold for DEGs is set at |log2 fold change (FC)| > 1 and p.adj (Benjamini & Hochberg) < 0.05."}, {"asset": "source:pmid:41196851", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "All statistical evaluations were conducted utilizing R software (version 4.2.1) in conjunction with GraphPad Prism 9 software."}, {"asset": "source:pmid:41196851", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "The determination of statistical significance for differences between groups and among multiple groups was carried out through the application of the t-test and one-way analysis of variance (ANOVA), respectively."}, {"asset": "source:pmid:41196851", "locator": "sections[6] \"Validation of hub gene expression in other datasets\" paragraph 2", "quote": "Perform diagnostic receiver operating characteristic (ROC) curve analysis with the pROC package and visualize the results using ggplot2."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the manuscript and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41196851", "locator": "sections[28] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the manuscript and its Supporting Information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Six hub genes—C3, CLEC4E, CSF3R, CXCR2, FPR2, and IDO1—were upregulated in the validation set and showed AUC values greater than 0.76, supporting their potential as diagnostic biomarkers for UAB.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41196851", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Receiver operating characteristic (ROC) curve analysis demonstrated that these six hub genes possess high diagnostic potential, with area under the curve (AUC) values greater than 0.76."}, {"asset": "source:pmid:41196851", "locator": "sections[18] \"Verification and diagnostic value of the 10 hub genes expression\" paragraph 2", "quote": "Based on the combined results of differential expression and ROC curve analyses, six hub genes—C3, CLEC4E, CSF3R, CXCR2, FPR2, and IDO1—were identified as potential biomarkers for UAB."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Six hub genes—C3, CLEC4E, CSF3R, CXCR2, FPR2, and IDO1—were upregulated in the validation set and showed AUC values greater than 0.76, supporting their potential as diagnostic biomarkers for UAB.", "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:41196851"], "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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Cells were cultured with penicillin/streptomycin at 37°C in 5% CO2. R"], "order_basis": "paper_text_order:2826", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["scription was done with Evo M-MLV RT Premix. qPCR was performed using SYBR® Green Premix Pro T", "as potential diagnostic biomarkers for UAB. qPCR validation of DEGs and functional assays.(A)", "validation of DEGs and functional assays.(A) qPCR validation of DEGs identified through CytoHu", ") Assessment of FPR2 knockdown efficiency by qPCR. 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