文献类型：期刊文献

中文题名：基于流行病学与网络毒理学探究邻苯二甲酸酯暴露与肝癌风险的相关性

英文题名：Association between phthalate exposure and liver cancer risk based on epidemiology and network toxicology

作者：罗慧英[1];王雪梅[1];杨佳瑶[1]

第一作者：罗慧英

机构：[1]甘肃中医药大学药学院,甘肃兰州730030

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2026

卷号：43

期号：3

起止页码：317

中文期刊名：环境与职业医学

外文期刊名：Journal of Environmental and Occupational Medicine

收录：;北大核心:【北大核心2023】；

语种：中文

中文关键词：邻苯二甲酸酯;肝癌;网络毒理学;尿苷-胞苷激酶2;6-磷酸葡萄糖脱氢酶;白蛋白

外文关键词：phthalates;liver cancer;network toxicology;uridine-cytidine kinase 2;glucose-6-phosphate dehydrogenase;albumin

摘要：[背景]肝癌是常见的恶性肿瘤之一。邻苯二甲酸酯(PAEs)作为一类广泛使用的增塑剂,可经多种途径参与肝脏疾病的发生与进展。[目的]探讨PAEs暴露与肝癌风险的相关性,为环境相关肿瘤风险事件的预防提供科学依据。[方法]采用卡方检验与多因素logistic回归分析美国国家健康与营养调查(NHANES)数据库中2001—2018年有关肝癌和PAEs的数据,探讨PAEs暴露与罹患肝癌的相关性。采用网络毒理学与机器学习相结合的方法筛选PAEs与肝癌相关的独立预后基因,并评估其与肿瘤免疫、肿瘤通路激活、肿瘤耐药性的相关性。最后通过GEO数据集、分子对接以及分子动力学模拟对预测结果进行验证。[结果]经筛选从NHANES数据库中获得符合要求的样本11378例,其中肝癌患者108例,健康对照11270例;经多因素logistic回归分析发现,9种PAEs暴露与肝癌发生风险呈正相关(OR>1,P<0.05)。网络毒理学研究发现,PAEs暴露与肝癌风险的相关作用与尿苷-胞苷激酶2(UCK2)、6-磷酸葡萄糖脱氢酶(G6PD)、白蛋白(ALB)3个独立预后基因有关。这3个独立预后基因不仅与肿瘤免疫微环境、肿瘤通路激活、肿瘤耐药性等具有显著相关性,彼此之间还存在复杂的相互作用。3个独立预后基因在验证数据集GSE58043与GSE115469中表达差异均有统计学意义(P<0.05)。分子对接与分子动力学模拟均证实,这3个独立预后基因可与PAEs自由结合并形成稳定复合物。[结论]PAEs暴露与肝癌风险呈正相关,两者的内在联系可能涉及物质代谢障碍、免疫抑制、炎症通路与肿瘤通路激活等。
[Background]Liver cancer is one of the common malignant tumors.Phthalates(PAEs),as a widely used class of plasticizers,can participate in the occurrence and progression of liver diseases through multiple pathways.[Objective]To explore the association between PAEs exposure and liver cancer risk and to provide a scientific basis for the prevention of environment-related tumor risk events.[Methods]Chi-square test and logistic regression were employed to analyze data from the National Health and Nutrition Examination Survey(NHANES)database between 2001 and 2018,to investigate the association between PAEs exposure and liver cancer.Network toxicology combined with machine learning was used to screen independent prognostic genes associated with PAEs and liver cancer,and to evaluate their correlations with tumor immunity,tumor pathway activation,and tumor drug resistance.Finally,the prediction results were validated using GEO datasets,molecular docking,and molecular dynamics simulations.[Results]After screening,11378 eligible samples were obtained from the NHANES database,including 108 patients with liver cancer and 11270 healthy controls.The logistic regression analysis revealed that exposure to nine types of PAEs was positively correlated with liver cancer(OR>1,P<0.05).The network toxicology analysis indicated that the association between PAEs exposure and liver cancer was related to three independent prognostic genes:uridine-cytidine kinase 2(uck2),glucose-6-phosphate dehydrogenase(G6PD),and albumin(ALB).These three independent prognostic genes were significantly associated with the tumor immune microenvironment,tumor pathway activation,and tumor drug resistance,and exhibited complex interactions with each other.All three independent prognostic genes showed significant differential expression in the validation datasets GSE58043 and GSE115469(P<0.05).The results of both molecular docking and molecular dynamics simulations confirmed that these three independent prognostic genes can freely bind to PAEs and form stable complexes.[Conclusion]Exposure to PAEs is positively correlated with liver cancer.The intrinsic association between the two may involve metabolic disorders,immunosuppression,and activation of inflammatory and tumor-related pathways.