对DEHP暴露和甲状腺癌的发展和进展的网络毒理洞察
1Department of Thyroid Surgery, Shanxi Provincial People's Hospital, Tai Yuan, China.
Frontiers in oncology
|September 3, 2025
概括
这项研究确定了与甲状腺癌风险相关的关键基因 (CYP1B1,GABRB2,TNFSF15) 以及与二乙烯甲酸盐 (DEHP) 接触后的结果. 这些发现为预防和治疗甲状腺癌提供了潜在的新目标.
科学领域:
- 环境毒理学
- 癌症学
- 生物信息学
背景情况:
- 二甲基甲酸 (DEHP) 是一种环境污染物,可能与各种癌症有关.
- 甲状腺癌是一个重要的全球健康问题,需要识别新的生物标志物来诊断和预后.
研究的目的:
- 鉴定与二乙基甲酸盐 (DEHP) 暴露相关的分子标记物及其与甲状腺癌发生和预后的相关性.
- 整合网络毒理学和分子对接方法来发现生物标志物.
- 使用公开可用的数据集验证已识别的标记.
主要方法:
- 使用癌症基因组图谱 (TCGA-THCA) 和基因表达总 (GEO) 数据集进行基因表达和临床数据.
- 进行了Venn图分析,以确定DEHP目标和甲状腺癌数据集之间的重叠基因.
- 进行基因本体学 (GO) 和基因和基因组的京都百科全书 (KEGG) 路径丰富分析.
- 使用多变量COX回归和Kaplan-Meier生存分析来识别中心基因和预后评估.
- 使用接收器操作特征 (ROC) 曲线验证候选基因.
- 应用分子对接来可视化DEHP与已识别的目标基因之间的相互作用.
主要成果:
- 发现了六个重叠的基因 (CYP1B1,ABCC3,KRT19,CUX2,GABRB2,TNFSF15).
- 证实CYP1B1,GABRB2和TNFSF15是具有显著高表达的候选枢纽基因.
- 这些枢纽基因的高表达与甲状腺癌患者的预后明显差 (p < 0. 05).
- 预后ROC曲线表明CYP1B1,GABRB2和TNFSF15具有强大的诊断潜力 (AUC> 0. 86).
- 分子对接可视化了DEHP及其目标基因之间的直接相互作用.
结论:
- 在DEHP暴露下,CYP1B1,GABRB2和TNFSF15被确定为与甲状腺癌发展和进展相关的显著分子标志物.
- 这些基因代表了甲状腺癌干预的潜在新型治疗点.
- 这项研究强调了网络毒理学和生物信息学在环境健康研究中的实用性.
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