使用基于网络的方法,构建诱导的肺癌不良结果途径框架
Cheng Cheng1, Bowen Fan1, Yi Yang1
1Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Suzhou Institute for Advanced Study of Public Health, Gusu School, Nanjing Medical University, Nanjing, Jiangsu 211166, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Ecotoxicology and environmental safety
|July 31, 2024
概括
像这样的环境污染物会增加肺癌的风险. 不良结果途径 (AOP) 框架通过分析基因,途径和细胞变化来帮助评估这种风险,有助于早期检测.
科学领域:
- 环境毒理学环境毒理学
- 癌症研究 癌症研究
- 计算毒理学计算毒理学
背景情况:
- 环境污染物与癌症有关,但风险评估方法有限.
- 不良结果路径 (AOP) 框架提供了一种结构化的方法来评估污染物诱导的瘤发生.
- 是已知的肺癌原体,但早期风险评估工具缺乏.
研究的目的:
- 应用AOP框架来评估引起的肺癌风险.
- 为了确定关键的基因,途径和事件,在肺癌的发展,由于暴露.
- 为评估环境污染物造成的肺癌风险提供计算模型.
主要方法:
- 对暴露和肺癌风险的系统审查.
- 生物信息分析用于识别使用考克斯和LASSO回归的风险基因.
- 使用Cytoscape构建一个计算AOP网络和框架.
- 外部验证使用酸盐诱导的细胞转化体外模型.
主要成果:
- 一项系统性审查证实,暴露于 (OR = 1.83) 的肺癌风险增加.
- 在AOP框架中,EGFR激活和PI3K/AKT通路信号是关键事件.
- 暴露促进了细胞增殖 (G1/S阶段过渡),导致肺癌.
- 外部验证支持模型在人类支气管上皮细胞中的发现.
结论:
- AOP框架有效地建模了引起的肺癌,整合了各种数据类型.
- 这种方法为评估与暴露相关的肺癌风险提供了有价值的见解.
- 应特别注意暴露于低剂量的人群.
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