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临床和基因组因素与前列腺癌中较大的瘤突变负担相关
Helen Y Hougen1, Ryon P Graf2, Gerald Li2
1Desai Sethi Urology Institute, University of Miami, Miami, FL, USA.
European urology open science
|September 4, 2023
概括
瘤突变负担 (TMB) 预测前列腺癌的免疫治疗反应. 膀和肝脏的转移显示出更高的TMB,而特定的基因变异和微卫星不稳定性也与增加的TMB相关.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 生物标志物 生物标志物
背景情况:
- 瘤突变负担 (TMB) 是预测各种癌症免疫检查点抑制剂治疗反应的关键生物标志物.
- 目前缺乏对影响前列腺癌TMB的基因组和临床因素的全面了解.
- 识别这些因素对于优化治疗策略和预测患者结果至关重要.
研究的目的:
- 在一大批前列腺癌标本中调查TMB水平的独立预测因子.
- 探索临床因素 (例如,治疗史,转移部位) 与TMB之间的相关性.
- 为了确定与前列腺癌中高TMB相关的特定基因组变化.
主要方法:
- 利用了包含来自2740个前列腺癌样本的数据的临床基因组数据库.
- 分析了与主要瘤部位相关的TMB水平,转移位置 (前列腺,淋巴结,骨,膀,肝脏) 以及安德روج因剥夺治疗的持续时间.
- 评估了微卫星不稳定状态和特定基因 (MLH1,MSH2,MSH6,BRCA2,CDK12,MRE11,PALB2) 的变化与TMB的关联.
主要成果:
- 膀,肝脏和其他部位的转移与前列腺相比显著更高的TMB有关.
- 高级和中级微卫星不稳定状态与TMB的增加密切相关.
- 包括MLH1,MSH2,MSH6,BRCA2,CDK12,MRE11和PALB2在内的基因的改变与更大的TMB有关.
- 使用24个月以上的雌激素剥夺治疗显示出与高TMB的弱相关性.
结论:
- 在前列腺癌的不同疗法中,TMB相对稳定.
- 转移部位和特定的遗传变化是TMB的重要预测因素.
- TMB可以作为一个有价值的生物标志物,用于指导诊断时或转移性前列腺癌晚期治疗决策.
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