Integrative analysis of thiamethoxam induced hepatocellular carcinoma toxicity mechanisms
Abstract Neonicotinoid (NEO) pesticides play a crucial role in agricultural production. However, their potential risks to human health and the environment cannot be overlooked. To gain a comprehensive understanding of the toxicity and mode of action of NEOs, thiamethoxam (THX), which exhibits the hi...
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Nature Portfolio
2025-07-01
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| author | Chenghao Wang Zhichao Wang Yinqin Hu Shi Xiang Hui Chen Chao Yang |
| author_facet | Chenghao Wang Zhichao Wang Yinqin Hu Shi Xiang Hui Chen Chao Yang |
| author_sort | Chenghao Wang |
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| description | Abstract Neonicotinoid (NEO) pesticides play a crucial role in agricultural production. However, their potential risks to human health and the environment cannot be overlooked. To gain a comprehensive understanding of the toxicity and mode of action of NEOs, thiamethoxam (THX), which exhibits the highest potential for carcinogenicity and hepatotoxicity, was selected as the subject of this study. We identified 61 intersection genes between THX targets and hepatocellular carcinoma (HCC)-related genes. These genes were then uploaded to the Metascape database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The GO analysis indicated that the significant biological processes mainly involved the response to xenobiotic stimuli, cellular response to chemical stress, cellular response to biotic stimuli, and response to toxic substances. The KEGG enrichment analysis pinpointed several key pathways, primarily including the cell cycle and Glycolysis/Gluconeogenesis. Subsequently, the intersection genes were imported into the Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO) databases to analyze expression differences, leading to the identification of 15 significantly differentially expressed core genes (SDECGs). By applying the Support Vector Machine (SVM) machine—learning model, we screened out five feature genes (CYP2C19, CYP3A4, FBP1, THBS4, CYP7A1) and constructed a nomogram. Molecular docking of THX with these five feature genes showed binding energies of less than −5 kcal/mol. This study offers a theoretical foundation for understanding the underlying mechanisms of THX-induced HCC. The findings provide a scientific basis for the safety assessment of THX in agricultural applications and contribute to the establishment of pesticide safety standards. |
| format | Article |
| id | doaj-art-02dbb09ed5fe46fdb033a9fa5023b0c0 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-02dbb09ed5fe46fdb033a9fa5023b0c02025-08-20T03:05:25ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-11792-3Integrative analysis of thiamethoxam induced hepatocellular carcinoma toxicity mechanismsChenghao Wang0Zhichao Wang1Yinqin Hu2Shi Xiang3Hui Chen4Chao Yang5Oncology Research Center, Jiangxi Provincial Key Laboratory of Traditional Chinese Medicine Diagnosis and Rehabilitation of Malignant Tumors, Jiangxi University of Chinese MedicineOncology Research Center, Jiangxi Provincial Key Laboratory of Traditional Chinese Medicine Diagnosis and Rehabilitation of Malignant Tumors, Jiangxi University of Chinese MedicineDepartment of Cardiovascular Disease, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineOncology Research Center, Jiangxi Provincial Key Laboratory of Traditional Chinese Medicine Diagnosis and Rehabilitation of Malignant Tumors, Jiangxi University of Chinese MedicineOncology Research Center, Jiangxi Provincial Key Laboratory of Traditional Chinese Medicine Diagnosis and Rehabilitation of Malignant Tumors, Jiangxi University of Chinese MedicineOncology Research Center, Jiangxi Provincial Key Laboratory of Traditional Chinese Medicine Diagnosis and Rehabilitation of Malignant Tumors, Jiangxi University of Chinese MedicineAbstract Neonicotinoid (NEO) pesticides play a crucial role in agricultural production. However, their potential risks to human health and the environment cannot be overlooked. To gain a comprehensive understanding of the toxicity and mode of action of NEOs, thiamethoxam (THX), which exhibits the highest potential for carcinogenicity and hepatotoxicity, was selected as the subject of this study. We identified 61 intersection genes between THX targets and hepatocellular carcinoma (HCC)-related genes. These genes were then uploaded to the Metascape database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The GO analysis indicated that the significant biological processes mainly involved the response to xenobiotic stimuli, cellular response to chemical stress, cellular response to biotic stimuli, and response to toxic substances. The KEGG enrichment analysis pinpointed several key pathways, primarily including the cell cycle and Glycolysis/Gluconeogenesis. Subsequently, the intersection genes were imported into the Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO) databases to analyze expression differences, leading to the identification of 15 significantly differentially expressed core genes (SDECGs). By applying the Support Vector Machine (SVM) machine—learning model, we screened out five feature genes (CYP2C19, CYP3A4, FBP1, THBS4, CYP7A1) and constructed a nomogram. Molecular docking of THX with these five feature genes showed binding energies of less than −5 kcal/mol. This study offers a theoretical foundation for understanding the underlying mechanisms of THX-induced HCC. The findings provide a scientific basis for the safety assessment of THX in agricultural applications and contribute to the establishment of pesticide safety standards.https://doi.org/10.1038/s41598-025-11792-3Hepatocellular carcinomaNeonicotinoid pesticideThiamethoxamNetwork toxicologyMachine learningMolecular docking |
| spellingShingle | Chenghao Wang Zhichao Wang Yinqin Hu Shi Xiang Hui Chen Chao Yang Integrative analysis of thiamethoxam induced hepatocellular carcinoma toxicity mechanisms Scientific Reports Hepatocellular carcinoma Neonicotinoid pesticide Thiamethoxam Network toxicology Machine learning Molecular docking |
| title | Integrative analysis of thiamethoxam induced hepatocellular carcinoma toxicity mechanisms |
| title_full | Integrative analysis of thiamethoxam induced hepatocellular carcinoma toxicity mechanisms |
| title_fullStr | Integrative analysis of thiamethoxam induced hepatocellular carcinoma toxicity mechanisms |
| title_full_unstemmed | Integrative analysis of thiamethoxam induced hepatocellular carcinoma toxicity mechanisms |
| title_short | Integrative analysis of thiamethoxam induced hepatocellular carcinoma toxicity mechanisms |
| title_sort | integrative analysis of thiamethoxam induced hepatocellular carcinoma toxicity mechanisms |
| topic | Hepatocellular carcinoma Neonicotinoid pesticide Thiamethoxam Network toxicology Machine learning Molecular docking |
| url | https://doi.org/10.1038/s41598-025-11792-3 |
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