关闭循环-膜-脂质平衡和囊泡运输链接DEHP暴露于子宫内膜异位症的证据
Yonggang Dai1, Lu Zhang1, Tian Wang1
1Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, No. 11 Middle Wuyingshan Road, Tianqiao District, Jinan City, Shandong Province, 250031, China.
暴露于二二甲基甲酸盐 (DEHP) 与子宫内膜异位症风险有关. 这项研究确定了参与脂质代谢和排毒的七个基因特征,为子宫内膜异位症提供了诊断和治疗的见解.
科学领域:
- 环境健康 环境健康
- 分子生物学分子生物学
- 计算生物学 计算生物学
背景情况:
- 子宫内膜异位症 (Ems) 的病因尚不清楚,环境暴露,如2-乙烯基) 甲酸盐 (DEHP) 与增加风险有关.
- 关联DEHP暴露与子宫内膜异位症的分子机制尚不清楚,阻碍了针对性的干预措施.
研究的目的:
- 确定将DEHP暴露与子宫内膜异位症连接的分子标和途径.
- 开发用于子宫内膜异位症诊断的基因特征,并确定潜在的治疗策略.
主要方法:
- 集成在的目标预测,转录组数据分析 (WGCNA,差异表达) 和蛋白质-蛋白质相互作用网络中.
- 应用可解释机器学习 (SHAP) 用于基因签名优先级,然后进行分子对接和动态模拟以进行验证.
主要成果:
- 确定了DEHP目标和子宫内膜异位症基因之间的17基因重叠,形成与脂质稳定,囊泡运输和解毒相关的子网络.
- 一个七个基因的签名 (ELOVL6,LYPLA1,UGT8,SLC1A5,HMGCR,EPHX1,VAMP2) 显示出高的诊断准确性 (AUC>0.75).
- 分子模拟证实了DEHP与UGT8,ELOVL6和HMGCR的稳定结合,支持它们在DEHP-子宫内膜异位症轴上的作用.
结论:
- 建立了一个全面的工作流程,从化学物质暴露到对子宫内膜异位症的验证分子标.
- 提出了一个DEHP-子宫内膜异位症监管框架,涉及脂质代谢,囊泡贩运和排毒.
- 这七个基因的特征为子宫内膜异位症分层提供了临床适用性,并突出了HMGCR和SLC1A5作为潜在的治疗点.
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