Wang Chenghao, Wang Zhichao, Hu Yinqin, Xiang Shi, Chen Hui, Yang Chao
Oncology Research Center, Jiangxi Provincial Key Laboratory of Traditional Chinese Medicine Diagnosis and Rehabilitation of Malignant Tumors, Jiangxi University of Chinese Medicine, Nanchang, 330004, People's Republic of China.
Department of Cardiovascular Disease, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, People's Republic of China.
Sci Rep. 2025 Jul 22;15(1):26544. doi: 10.1038/s41598-025-11792-3.
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.
新烟碱类（NEO）农药在农业生产中发挥着关键作用。然而，它们对人类健康和环境的潜在风险不容忽视。为了全面了解新烟碱类农药的毒性和作用模式，本研究选择了具有最高致癌性和肝毒性潜力的噻虫嗪（THX）作为研究对象。我们确定了THX靶点与肝细胞癌（HCC）相关基因之间的61个交集基因。然后将这些基因上传到Metascape数据库进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。GO分析表明，显著的生物学过程主要涉及对外源生物刺激的反应、细胞对化学应激的反应、细胞对生物刺激的反应以及对有毒物质的反应。KEGG富集分析确定了几个关键途径，主要包括细胞周期和糖酵解/糖异生。随后，将交集基因导入基因表达谱交互式分析（GEPIA）和基因表达综合数据库（GEO）以分析表达差异，从而鉴定出15个显著差异表达的核心基因（SDECGs）。通过应用支持向量机（SVM）机器学习模型，我们筛选出五个特征基因（CYP2C19、CYP3A4、FBP1、THBS4、CYP7A1）并构建了列线图。THX与这五个特征基因的分子对接显示结合能小于-5千卡/摩尔。本研究为理解THX诱导HCC的潜在机制提供了理论基础。这些发现为THX在农业应用中的安全性评估提供了科学依据，并有助于建立农药安全标准。
