Phthalate exposure and hepatocellular carcinoma: Unraveling mechanisms through network toxicology.

IF 4.6 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology Pub Date : 2025-12-01 Epub Date: 2025-07-26 DOI:10.1016/j.tox.2025.154243

Simin Zhan, Chun Li, Kaiyi Zeng, Yanhao Ran, Chenyu Liu, Yunshuo Zhang, Zekai Zeng, Chuntian Wang, Ziqing Yang

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引用次数: 0

Abstract

Phthalates are typical environmental pollutants that, as plasticizers, are released into the environment through waste, accumulate in organisms, and have reproductive toxicity and potential carcinogenic risks. However, the specific regulatory mechanisms by which phthalates induce liver cancer are still unclear. This study investigates the role of CYP2C9 in liver cancer (LIHC) and its interaction with plasticizers such as BBP and DBP. Toxicological analyses reveal that CYP2C9 is significantly downregulated in LIHC, correlating with poorer patient survival rates. Differential expression analysis using TCGA and GTEx databases confirms high CYP2C9 expression in liver cells, negatively associated with immune cell infiltration. Methylation and mutation analyses indicate a significant relationship between CYP2C9 expression and methylation levels. Additionally, molecular dynamics simulations demonstrate strong binding stability between CYP2C9 and BBP. These findings underscore the critical role of CYP2C9 in liver cancer progression and support its potential as a therapeutic target.

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邻苯二甲酸盐暴露与肝细胞癌：通过网络毒理学揭示机制。

邻苯二甲酸盐是典型的环境污染物，作为增塑剂通过废物释放到环境中，在生物体中积累，具有生殖毒性和潜在的致癌风险。然而，邻苯二甲酸酯诱发肝癌的具体调控机制尚不清楚。本研究探讨CYP2C9在肝癌（LIHC）中的作用及其与BBP和DBP等增塑剂的相互作用。毒理学分析显示，CYP2C9在LIHC中显著下调，与较差的患者生存率相关。使用TCGA和GTEx数据库进行差异表达分析，证实CYP2C9在肝细胞中高表达，与免疫细胞浸润呈负相关。甲基化和突变分析表明CYP2C9表达与甲基化水平之间存在显著关系。此外，分子动力学模拟表明CYP2C9与BBP之间具有很强的结合稳定性。这些发现强调了CYP2C9在肝癌进展中的关键作用，并支持其作为治疗靶点的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology 医学-毒理学

CiteScore

7.80

自引率

4.40%

发文量

222

审稿时长

23 days

期刊介绍： Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.