特定亚型的昼夜时钟失调调节乳腺癌生物学,侵袭性和预后
Jan A Hammarlund1, Shi-Yang Li2, Gang Wu3
1School of Biomedical Engineering, Science and Health Systems. Drexel University, Philadelphia, PA, USA.
bioRxiv : the preprint server for biology
|June 9, 2023
概括
乳腺癌中的循环节障碍与特定的亚型有关,这些亚型会影响表皮-介质细胞转换 (EMT) 途径. 这种分子时钟失调会影响转移潜力和患者预后,突出治疗点.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 在瘤学瘤学.
背景情况:
- 循环节障碍与乳腺癌风险有关,但人类乳腺组织中的分子节奏仍然不太了解.
- 研究人类非癌症和癌症乳腺组织中的分子节奏对于了解乳腺癌的发展和进展至关重要.
研究的目的:
- 研究人类非癌症和癌症乳腺组织中的分子节奏.
- 探索昼夜干扰,上皮层-介质细胞过渡 (EMT) 和乳腺癌预后之间的关系.
主要方法:
- 使用时间标记的活检和公共数据集进行分子节律的信息化重建.
- 对非癌症和各种乳腺癌亚型的昼夜基因表达的分析.
- 评估CYCLOPS大小和EMT途径在光线A瘤中的循环.
主要成果:
- 在非癌性组织中推断的昼夜基因顺序与已知的生理学保持一致,与炎症,EMT和雌激素通路的昼夜调制保持一致.
- 乳腺瘤在昼夜组织中表现出亚型特定的变化.
- 光线A瘤表现出中断但持久的节奏,在高幅度瘤中增加了EMT基因循环.
- 高幅度的Luminal A瘤与5年生存率的降低相关.
- 在3D Luminal A培养中破坏分子时钟减少了入侵.
结论:
- 这项研究揭示了乳腺癌中亚型特定的昼夜干扰,将其与EMT,转移潜力和患者预后联系起来.
- 在Luminal A培养物中分子时钟的破坏减少了入侵,这表明昼夜调节在乳腺癌转移中的作用.
- 这些发现突显了光线A乳腺瘤中全局节律强度 (CYCLOPS大小) 的预后意义.
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