DDR2-COL11A1转录合作为结肠直肠癌的候选治疗标:综合转录和深度学习验证
Yasemin Başbınar1, Ömer Akgüller2,3, Asım Leblebici4
1Department of Translational Oncology, Oncology Institute, Dokuz Eylul University, Izmir 35340, Turkey.
迪斯科伊丁域受体2 (DDR2) 通过加强与COL11A1.1.的转录合来驱动结直肠癌的进展. 这种机制增强了原沉积和矩阵重塑,提供了超出受体丰度的新治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 细胞外基质 (ECM) 改造对于结直肠癌 (CRC) 的进展至关重要.
- 在CRC中,ECM组件和矩阵金属蛋白酶的转录调节尚未完全理解.
研究的目的:
- 在结肠直肠瘤发生过程中研究迪斯科丁域受体 (DDR) 介导的转录网络.
- 阐明DDR1和DDR2在协调CRC进展期间ECM重塑中的作用.
主要方法:
- 在正常,腺瘤和癌症阶段对680个样本进行综合计算分析.
- 途径基因和深度神经网络分类的阶段分层相关性分析.
- SHAP分析以确定癌症分类的关键基因相互作用.
主要成果:
- DDR2显示显著加强了与通路基因的相关性,从正常到癌症,而不是DDR1.1.
- DDR2-COL11A1合在癌症中显著加剧,导致COL11A1表达的增加.
- 尽管DDR2表达稳定,但路径激活发生,突出显示了增强的转录合效率.
- 深度神经网络在区分CRC阶段方面实现了93.14%的准确性,其中DDR2-COL11A1被确定为关键相互作用.
结论:
- 特定于DDR2的转录合是结直肠癌进展的关键机制.
- COL11A1是一个关键的下游目标,通过DDR2介导合来调节.
- 针对合效率的治疗策略,而不仅仅是受体丰度,可能有利于CRC治疗.
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