解读BDCPP的致病机制 通过结合网络毒理学,机器学习和分子对接的综合方法,通过子宫内膜癌进展中的暴露
Zhichao Wang1, Yinjie Fu, Qiqi Cai
1Jiangsu Key Laboratory for Biodiversity and Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China.
International journal of surgery (London, England)
|September 24, 2025
概括
环境污染物1,3-二二) 酸盐 (BDCPP) 与子宫内膜癌 (EC) 有关. 这项研究确定了八个关键基因和途径参与BDCPP诱导的EC,提供了对其机制的见解.
科学领域:
- 环境健康 环境健康
- 在瘤学瘤学.
- 毒理学 毒理学 毒理学
背景情况:
- 子宫内膜癌 (EC) 是一种流行的妇科恶性瘤,越来越多的证据将环境污染物与其发展联系在一起.
- 在流行病学研究中,一种环境化学物质 - - 双二二酸 (BDCPP) 与EC的风险增加有关.
- 基于BDCPP诱导的EC的特定分子标和机制在很大程度上仍未被探索.
研究的目的:
- 确定关键基因 (枢纽基因) 并阐明涉及到由1,3-二chloro-2-propyl) 酸盐 (BDCPP) 诱导的子宫内膜癌发育的潜在分子机制.
- 开发BDCPP暴露在子宫内膜癌患者中的风险预测模型.
主要方法:
- 公共数据库的综合分析,以确定BDCPP和EC的共同目标.
- 构建一个蛋白质-蛋白质相互作用 (PPI) 网络,并应用机器学习来精确定位枢纽基因.
- 进行了丰富分析 (GO,KEGG,Reactome) 和单基因基因组丰富分析 (GSEA).
- 分子对接被用来预测BDCPP与已识别的枢纽基因的结合亲和力.
主要成果:
- 确定了165个潜在的目标,从而确定了八个枢纽基因:PLA2G2A,PLAU,SIRT2,DRD2,GSK3A,THRB,CYP17A1和TLR9.
- 开发了一个BDCPP暴露风险评分模型,在预测EC患者预后方面表现出适度的准确性.
- 分子对接证实了BDCPP与这些枢纽基因的结合潜力,涉及炎症激活,荷尔蒙干扰,脂质代谢和病变发生的表观遗传失调.
结论:
- 这项研究成功地确定了关键的枢纽基因,并阐明了参与BDCPP诱导的子宫内膜癌的关键分子途径.
- 这些发现为环境污染物在EC病原发生中的作用提供了新的见解,并为研究其他化学致癌物提供了框架.
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