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Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
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在临床队列中验证在体外训练的转录组放射性敏感性签名.

John D O'Connor1, Ian M Overton1, Stephen J McMahon1

  • 1Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, UK.

Cancers
|July 14, 2023
PubMed
概括
此摘要是机器生成的。

转录基因放射性敏感性标志在临床环境中显示出不良的可复制性. 不同的正常化方法显著影响预测,而已发表的签名不能可靠地预测放射治疗 (RT) 患者的结果.

关键词:
基因签名 基因签名 基因签名辐射敏感性 辐射敏感性翻译学 翻译学 翻译学 翻译学

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科学领域:

  • 在瘤学瘤学.
  • 基因组学就是基因组学.
  • 生物信息学是一种生物信息学.

背景情况:

  • 放射治疗 (RT) 的转录组个性化是一个不断发展的领域.
  • 之前的体外研究表明,独立模型的性能不佳.
  • 在临床环境中,放射性敏感性信号的可复制性需要进行彻底的评估.

研究的目的:

  • 评估已发表的放射敏感性信号的临床可重现性.
  • 评估微阵列规范化方法对放射敏感性预测的影响.
  • 在临床队列中比较签名与对照模型的性能.

主要方法:

  • 使用不同的规范化方法评估放射性敏感性预测之间的一致性.
  • 在临床队列中从重新采样的体外数据中进行基准对照签名.
  • 在临床转录基因数据上进行了生存分析和基因组丰富分析.

主要成果:

  • 规范化方法显著影响了放射性敏感性指数 (RSI) 值,一致性极限超过20%.
  • 没有公布的签名显示出与重新采样的对照对预测临床结果的显著改善.
  • 包括增殖和免疫反应在内的重叠的生物过程与RT治疗和非RT治疗患者的癌症结局有关.

结论:

  • 不同的规范化方法是不可互换的,并影响辐射敏感性预测.
  • 由于与一般癌症结果基因的重叠,已发表的放射性敏感性签名的临床实用性仍然不确定.
  • 现有的签名可能缺乏特异性,因为影响结果的关键生物过程在放射治疗和未治疗的患者之间共享.