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pmid:41130017
Exploring the therapeutic role of thiabendazole in lung adenocarcinoma via network pharmacology and single-cell analysis.
Wanghong Qi · Guoqiu Xu · Lang Tang · Chunlin Ye · Xi Liu
Translational oncology · 2025 doi:10.1016/j.tranon.2025.102548
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Experiment
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Data
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Complete file
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Despite advances in targeted therapies, challenges such as drug resistance and severe side effects persist. Thiabendazole, an antiparasitic drug, has shown potential anticancer effects in LUAD.\nMETHODS: This study used network pharmacology, integrating single-cell RNA sequencing (scRNA-seq) data (GSE136103), GEO transcriptome datasets (GSE10072, GSE19188, GSE19804, GSE30219, GSE40791), and bioinformatics tools to explore Thiabendazole's mechanisms in LUAD. Potential targets were predicted through PubChem and SwissTargetPrediction. scRNA-seq data were analyzed using Seurat, and key genes and pathways were identified via Weighted Gene Co-expression Network Analysis (WGCNA) and multi-omics integration. Diagnostic genes were further screened using LASSO regression, Support Vector Machine (SVM), and random forest (RF) models.\nRESULTS: Single-cell analysis revealed macrophages as key targets of Thiabendazole. Transcriptomic analysis identified 2034 downregulated and 2388 upregulated genes. WGCNA found a core gene module (MEred) strongly correlated with Thiabendazole (r = 0.75, p = 2e-07). Four diagnostic genes-ACE, ALDOA, MME, and PMP22-showed high accuracy (0.982). Thiabendazole also modulated immune cell infiltration, particularly affecting macrophage activity. Molecular docking confirmed stable binding to ACE, ALDOA, and MME.\nCONCLUSION: Thiabendazole demonstrates promising anticancer potential in LUAD, influencing key genes and immune pathways. 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