肥胖和胃癌之间的因果关系和共同的分子特征:一个大规模的门德尔随机化和多omics分析
Abao Xing1,2, Henry H Y Tong1, Songyan Liu3
1Centre for Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences, Macao Polytechnic University, Macao, Macao SAR, China.
Frontiers in oncology
|November 13, 2023
概括
肥胖导致胃癌风险增加,原因是AKT1,IL-6和TNF信号的增加. 氨酸可能提供一种预防策略来应对这种过渡.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 在瘤学瘤学.
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 观察性研究表明,肥胖是胃癌的风险因素,但因果关系尚未被证明.
- 了解肥胖和胃癌之间的分子联系对于预防至关重要.
研究的目的:
- 为了确定肥胖和胃癌之间的因果关系.
- 确定共享的分子通路和生物标志物,将肥胖与胃癌联系起来.
主要方法:
- 使用GWAS数据进行双样本孟德尔随机化 (MR) 分析.
- 生物信息学和多组学元分析 (蛋白质组,转录组).
- 在患者血和药物查 (SBVS) 中发现的临床验证.
主要成果:
- 核磁共振分析证实肥胖和胃癌之间存在显著的因果关系 (OR=1.37,P=0.0028).
- 发现了TNF,PI3K-AKT和细胞因子信号传递通路的共享失调,并对AKT1,IL-6和TNF进行了上调.
- 临床验证显示,在这两种疾病中,炎症标志物升高;腺被确定为潜在的AKT1抑制剂.
结论:
- 肥胖导致胃癌风险增加,通过AKT1/IL-6/TNF通路激活的介导.
- 氨酸通过抑制AKT1显示出作为预防剂的潜力,减轻与肥胖相关的胃癌风险.
- 这些发现支持在肥胖个体中治疗胃癌的新型预防性药物开发.
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