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瘤原始细胞无甲基组和碎片组的早期变化预测了布罗利祖马布治疗的固体瘤的结果
Eric Y Stutheit-Zhao1, Enrique Sanz-Garcia1, Zhihui Amy Liu1
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Cancer discovery
|February 23, 2024
概括
细胞自由甲基化DNA (cfMeDIP-seq) 的早期变化可以预测患者接受pembrolizumab治疗的结果. 这种无瘤方法分析甲基化和碎片长度,提供了一种监测癌症患者的新方法.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 生物标志物 生物标志物
背景情况:
- 循环瘤DNA (ctDNA) 动力学预测了对pembrolizumab的反应,但通常需要瘤组织测序.
- 现有的ctDNA方法通常依赖于瘤信息或固定基因面板.
研究的目的:
- 开发和验证使用甲基组学和碎片组学进行瘤原始,突变不可知ctDNA测定.
- 评估这种新型ctDNA方法对 pembrolizumab 治疗结果的预测价值.
主要方法:
- 使用无细胞甲基化DNA免疫沉和测序 (cfMeDIP-seq) 进行全基因组甲基化和片段长度分析,对87名患有高级固体瘤的患者的血样本进行了分析.
- 训练泛癌甲基化特征以量化癌症特异甲基化 (CSM) 和片段长度得分 (FLS).
- 分析CSM和FLS的早期动力学与治疗反应,整体存活率 (OS) 和无进展存活率 (PFS) 相比.
主要成果:
- CSM和FLS与瘤告知ctDNA水平有很强的相关性.
- 早期的CSM动力学独立预测了整个瘤类型的OS和PFS,无论PD-L1状态或瘤突变负担如何.
- 早期FLS的动力学与OS独立于CSM有关.
结论:
- 结合甲基组学和碎片组学的瘤原始ctDNA方法可以预测用pembrolizumab治疗的患者的结果.
- 早期CSM和FLS的变化是治疗反应和生存的强有力的生物标志物.
- 这种方法为ctDNA分析提供了一个有希望的替代方案,而不需要匹配的瘤组织.
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