ArticleCurrent topics in medicinal chemistry2026
Macrophage-related GBP4 as a Novel Biomarker for Crohn's Disease: Insights from WGCNA, Mendelian Randomization, and Immunohistochemical Validation.
Article in Current topics in medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionCrohn's disease (CD) is a complex inflammatory bowel disorder with incompletely understood mechanisms. This study aimed to identify novel biomarkers and elucidate macrophage-related pathogenesis in CD.
methodsUsing gene expression data (GSE17928522) from the Gene Expression Omnibus (GEO) database, we compared 1135 CD patients with 180 healthy controls to identify altered gene expression profiles. Immune infiltration analysis was conducted to evaluate changes in immune cell subpopulations. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct gene co-expression networks and identify macrophage-associated modules. Mendelian randomization was used to validate the causal role of macrophages. For ex vivo validation, immunohistochemical staining of GBP4 protein expression was performed in colonic tissue samples from 6 CD patients (with ileal or colonic lesions). Non-lesional tissues from the same patients served as intra-individual controls to minimize inter-patient variability.
resultsOur analysis revealed significant changes in immune cell subpopulations, particularly macrophages, within the CD microenvironment. A macrophage-associated module was identified, with GBP4 emerging as a critical gene. Immunohistochemical staining confirmed differential expression of GBP4 in CD tissue samples compared to controls. DISCUSSION: This multi-modal study establishes GBP4 as a novel macrophage-associated biomarker for CD, supported by causal Mendelian randomization and immunohistochemical validation. The integration of WGCNA and genetic evidence strengthens the role of macrophage dysregulation in CD pathogenesis. Limitations include population bias in genomic data and small validation cohorts, but the consistency across methodologies underscores GBP4's potential as a therapeutic target.
conclusionOur findings highlight GBP4 as a novel potential biomarker and therapeutic target in CD, providing insights into the immune-mediated mechanisms underlying the disease. These results contribute to a better understanding of CD pathogenesis and may lead to new therapeutic strategies.
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