在转移性割敏感前列腺癌中PIK3/Akt/mTOR通路的改变
Philip Sutera1, Jongmyung Kim2, Ritesh Kumar2
1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland, USA.
The Prostate
|July 18, 2024
概括
在转移性割敏感前列腺癌 (mCSPC) 中,PIK3/Akt/mTOR通路的改变是常见的,并且与更糟糕的结局有关. 这些遗传变化也改变了瘤.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 在转移性割敏感前列腺癌 (mCSPC) 中,PIK3/Akt/mTOR通路经常发生变化.
- 这些mCSPC变化的预后影响和遗传情景尚不清楚.
研究的目的:
- 调查mCSPC中PIK3/Akt/mTOR路径变化的预后意义.
- 描述与这些变化相关的遗传场景.
主要方法:
- 对472名mCSPC患者进行了下一代测序.
- PIK3/Akt/mTOR通路的改变包括关键基因 (Akt1,mTOR,PIK3CA,PIK3CB,PIK3R1,PTEN,TSC1,TSC2) 的突变.
- 使用卡普兰-梅尔和考克斯回归分析评估了无放射性进展生存率 (rPFS),割抵抗时间 (tdCRPC) 和整体生存率 (OS).
主要成果:
- 31.9%的患者有PIK3/Akt/mTOR路径的改变.
- 变化与割耐药性 (tdCRPC) (HR 1.43,p=0.02) 的较短时间相关,但与无放射性进展生存率 (rPFS) (HR 1.20,p=0.21) 相关.
- PIK3/Akt/mTOR改变的瘤经常与TP53和TMPRSS2-ERG突变同时发生,并显示了p53信号和血管生成途径的丰富.
结论:
- 在mCSPC中,PIK3/Akt/mTOR通路的改变很普遍,表明预后较差.
- 具有这些变化的瘤的遗传特征与野生型瘤有显著差异.
- 需要进一步的研究来阐明和准mCSPC治疗策略中的PIK3/Akt/mTOR途径.
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