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准Nrf2/PHKG2轴以提高NSCLC中的放射敏感性

Fushi Han^1,2, Shuzhen Chen³, Kangwei Zhang^1,2

¹Department of Medical Imaging, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.

NPJ precision oncology

|August 21, 2024

概括

这项研究揭示了NRF2/PHKG2通路如何调节非小细胞肺癌 (NSCLC) 放射治疗诱导的铁亡. 向NRF2可以增强PHKG2的表达,增加铁亡并改善NSCLC的放射敏感性.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
癌症研究癌症研究

背景情况:

铁化是一种有前途的抗癌策略,但其在非小细胞肺癌 (NSCLC) 中的机制尚未完全理解.
放射治疗耐药性是NSCLC治疗的一个重大挑战.
识别新的分子标对于改善NSCLC治疗结果至关重要.

研究的目的:

通过NRF2/PHKG2轴阐明NSCLC中放射治疗诱导的铁亡的调节机制.
调查PHKG2在NSCLC辐射敏感性和放射电阻中的作用.
开发基于铁亡相关基因的NSCLC患者的预后模型.

主要方法:

高通量转录组测序和拉索风险回归分析以识别与铁亡相关的基因.
对临床NSCLC样本的分析,以评估放射治疗后PHKG2表达变化.
在NSCLC细胞和瘤模型中的体外和体内实验,以评估NRF2/PHKG2轴的功能.

主要成果:

拉索风险回归模型结合了与铁相关的基因,准确预测了NSCLC患者的预后.
在放射治疗敏感的NSCLC组织中观察到PHKG2表达的增加.
通过增加细胞内铁和线粒体应激,PHKG2的过度表达增强了放射治疗诱导的铁,而NRF2被发现可以通过转录抑制PHKG2.

结论:

NRF2/PHKG2轴在NSCLC中调节铁和放射敏感性方面发挥着至关重要的作用.
向NRF2以上调PHKG2显示了通过促进铁亡来克服NSCLC中放射治疗耐药性的潜力.
开发的FAGs-Lasso风险回归模型为NSCLC患者预后提供了有价值的工具.

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