环境污染对人体健康的影响：探讨多环芳烃在儿童骨肉瘤中的作用。

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety Pub Date : 2025-07-19 DOI:10.1016/j.ecoenv.2025.118693

Mingxian Xu , Yu Xu , Yaping Huang , Jixiang Shi , Lifeng Yin , Jian Tu , Junqiang Yin , Changye Zou

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引用次数: 0

摘要

背景：多环芳烃（PAHs）是公认的环境致癌物，广泛通过工业过程和汽车尾气排放。尽管多环芳烃暴露与各种恶性肿瘤有关，但其参与儿童骨肉瘤的具体分子机制仍不清楚。方法：本研究分析了2000年至2019年间诊断的345例儿童骨肉瘤患者的居住和环境数据，以探索环境多环芳烃暴露的潜在相关性。从生物信息学数据库（PubChem， STITCH, GeneCards, DisGeNET）中检索到1617个候选pah相关分子靶点，并使用STRING和Cytoscape网络分析确定核心靶点。通过分子对接来评估选定的靶点与两种主要的多环芳烃化合物萘（NAP）和苯并[a]芘（BaP）之间的相互作用。同时，对41例患者的血清多环芳烃- dna加合物浓度进行了量化，并对其与居住地和临床结果的关系进行了研究。结果：将初步候选名单细化为14个核心分子靶点。其中，ACTB、EGFR和JUN通过生存分析和机器学习模型被确定为关键的预后基因。这些基因在致癌通路中富集，包括PI3K-Akt信号通路。分子对接证实NAP/BaP与三个核心靶点之间存在较强的结合亲和力。临床上，高度城市化地区的患者血清多环芳烃- dna加合物水平明显高于欠发达地区（443.9 pg/mL vs. 146.4 pg/mL, p ）。结论：本研究首次在系统水平上研究了多环芳烃暴露与儿童骨肉瘤之间的潜在分子机制。ACTB、EGFR和JUN作为环境响应性致癌介质的鉴定为未来的验证提供了一个机制框架。这些发现支持了计算毒理学在环境风险评估中的应用，并强调了预防和治疗儿童骨肉瘤的潜在分子靶点。

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Impact of environmental pollution on human health: Investigating the role of Polycyclic Aromatic Hydrocarbons in pediatric osteosarcoma

Background

Polycyclic aromatic hydrocarbons (PAHs), widely emitted through industrial processes and vehicular exhaust, are recognized environmental carcinogens. Although PAH exposure has been linked to various malignancies, the specific molecular mechanisms underlying its involvement in pediatric osteosarcoma remain poorly defined.

Methods

This study analyzed residential and environmental data from 345 pediatric osteosarcoma patients diagnosed between 2000 and 2019 to explore potential correlations with environmental PAH exposure. A total of 1617 candidate PAH-associated molecular targets were retrieved from bioinformatics databases (PubChem, STITCH, GeneCards, DisGeNET), and core targets were identified using STRING and Cytoscape network analyses. Molecular docking was conducted to assess interactions between selected targets and two major PAH compounds, naphthalene (NAP) and benzo[a]pyrene (BaP). In parallel, serum PAHs-DNA adduct concentrations were quantified in 41 patients, and their associations with residential location and clinical outcomes were examined.

Results

The analysis refined the initial candidate list to 14 core molecular targets. Among these, ACTB, EGFR, and JUN were identified as key prognostic genes through survival analysis and machine learning models. These genes were enriched in oncogenic pathways, including the PI3K-Akt signaling pathway. Molecular docking confirmed strong binding affinities between NAP/BaP and the three core targets. Clinically, serum PAHs-DNA adduct levels were significantly higher in patients from highly urbanized areas compared to less developed regions (443.9 pg/mL vs. 146.4 pg/mL, p < 0.0001) and were associated with reduced overall survival (p = 0.0091).

Conclusion

This study presents the first systems-level investigation elucidating potential molecular mechanisms linking PAH exposure to pediatric osteosarcoma. The identification of ACTB, EGFR, and JUN as environmentally responsive oncogenic mediators offers a mechanistic framework for future validation. These findings support the utility of computational toxicology in environmental risk assessment and highlight potential molecular targets for the prevention and treatment of pediatric osteosarcoma.

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来源期刊

Ecotoxicology and Environmental Safety 环境科学-毒理学

CiteScore

12.10

自引率

5.90%

发文量

1234

审稿时长

88 days

期刊介绍： Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.