Exploring the therapeutic role of thiabendazole in lung adenocarcinoma via network pharmacology and single-cell analysis
Year: 2025
Type: article
Abstract: • Thiabendazole shows anticancer potential in lung adenocarcinoma by modulating tumor–immune interactions. • Single-cell analysis identifies macrophages as key cellular targets of Thiabendazole. • Multi-omics and machine learning reveal four core diagnostic genes: ACE, ALDOA, MME, PMP22. • Thiabendazole reshapes immune infiltration and regulates pathways linked to inflammation and metabolism. • Functional studies confirm ALDOA as a driver of LUAD proliferation and survival. Lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths globally, with over 2.2 million new cases in 2020. 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. 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. 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. Thiabendazole demonstrates promising anticancer potential in LUAD, influencing key genes and immune pathways. It may serve as an effective therapeutic agent targeting both cancer cells and the tumor microenvironment.
Source: Translational Oncology
Authors: Wanghong Qi, Guoqiu Xu, Lang Tang, Chunlin Ye, Xi Liu
Institution: First Affiliated Hospital of Nanchang University
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,390
OpenAlex ID: W4415428504