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在APC驱动的结直肠癌发生过程中,WNT/PI3K-mTOR轴与微生物群之间的相互作用:来自试点研究的数据和对预防CRC的可能影响
Floriana Jessica Di Paola1, Chiara Alquati2,3, Gabriele Conti4
1IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. floriana.dipaola2@unibo.it.
Wnt/β-catenin和PI3K/mTOR通路相互作用在结直肠癌 (CRC) 和家族腺瘤多重症 (FAP) 中发生变化. 特定的肠道细菌特征与这些路径变化相关,提供新的CRC生物标志物.
科学领域:
- 在瘤学瘤学.
- 微生物学 微生物学
- 分子生物学分子生物学
背景情况:
- Wnt/β-catenin信号损害导致85%的结直肠癌 (CRC).
- 改变PI3K/mTOR通路和肠道微生物群也会导致CRC的发展.
- 了解这些途径和微生物群在CRC进展中的相互作用至关重要.
研究的目的:
- 研究Wnt/β-catenin和PI3K/mTOR通路之间的相互作用.
- 分析这些途径与肠道微生物群组成之间的关联.
- 确定潜在的生物标志物用于结直肠癌的预防和治疗.
主要方法:
- 使用RT-qPCR和IHC.使用Wnt/β-catenin和PI3K/mTOR通路蛋白质和基因的分析.
- 下一代测序 (NGS) 和桑格测序用于CRC相关突变.
- 16S rRNA测序用于口腔,便和粘膜微生物群的概况.
主要成果:
- 与CRC相比,在家族性腺瘤多重症 (FAP) 病变中观察到Wnt/β-catenin和PI3K/mTOR通路的同时过度激活.
- 在FAP中发现了Wnt/β-catenin标记物和肠道细菌 (Clostridium_sensu_stricto_1, Bacteroides) 之间的特定相关性.
- 在FAP便和腺瘤中丰富某些细菌 (Alistipes,Lachnospiraceae,Ruminococcaceae,Lachnoclostridium),其中Lachnoclostridium与cMYC相关.
- 在PI3K/mTOR突变的CRC中,p-S6R与Fusobacterium和Dialister相关.
结论:
- 这项研究揭示了Wnt/β-catenin和PI3K/mTOR通路之间的相互作用.
- 这些通路的异常与FAP和CRC患者的特定微生物群特征相关.
- 确定了潜在的新生物标志物和治疗点,用于预防CRC,早期检测腺瘤和治疗.
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