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pmid:39525307
Exploring the Role of Inflammatory Genes and Immune Infiltration in Vestibular Schwannomas Pathogenesis.
Jinlu Gan · Yanling Zhang · Deqiang Lei · Yingchun Zhou · Hongyang Zhao · Lei Wang
Journal of inflammation research · 2024 doi:10.2147/JIR.S476745
Paper
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Experiment
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Data
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Analysis
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Complete file
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Recent research has offered insights into the inflammatory microenvironment in modulating tumor dynamics. This study investigates the role of inflammatory genes and immune infiltration in VS pathogenesis.\nMethods: We retrieved mRNA microarray data of VSs and normal nerves from the GEO database (GSE141801, GSE108524, and GSE56597), focusing on bioinformatic analysis of inflammatory response genes. Based on the evidence provided by bioinformatics analysis, we assessed the expression levels of Iba-1, IL-10, IL-10RA, and IL-18 in 31 VS patients via immunohistochemistry and delved into their association with tumor size and auditory dysfunction.\nResults: We identified 1117 differentially expressed genes (DEGs) in VSs compared to normal nerves, showing an upregulation in inflammatory pathways. Intersection with inflammatory response genes (IRG) yielded 41 significant IRG-DEGs. Network analysis identified a core module of 10 IRG-DEGs and 11 hub genes, most of which were inflammatory cytokines. Immune infiltration analysis showed macrophage activation and M2 polarization. These findings were validated in an independent dataset (GSE39645). To further explore the association between inflammation and tumor behaviors, immunohistochemistry analysis was conducted on VS samples and the results exhibited notable associations between the macrophage marker (Iba1) and inflammatory cytokines (IL-10, IL-10RA, and IL-18) with both tumor size and auditory dysfunction. In particular, the multiple regression analysis of inflammatory cytokines demonstrated that IL-10 and IL-10RA were statistically significant predictors of tumor size, while IL-18 was associated with hearing loss.\nConclusion: Our study underscores the role of inflammation in VS pathogenesis, showing that macrophage activation with M2 polarization and the expression of inflammatory cytokines, especially IL-10/IL-10RA and IL-18, are linked to tumor size and auditory function. 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In the immunohistochemistry analysis, statistical analyses were performe"], "order_basis": "paper_text_order:738", "id": "assay:1"}, {"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["ols_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Given the intricacies of real-world data, we further conducted the multiple regression analysis of inflammatory cytokines to distill their interaction effects."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}