遗传多态性和瘤突变特征胜过晚期结肠直肠癌患者的生存:一项探索性研究
Juan Pablo Cayún1,2, Leslie Carol Cerpa1,2, Alicia Colombo3,4
1Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago 8350499, Chile.
Current oncology (Toronto, Ont.)
|January 22, 2024
概括
在DPYD,ABCB1和MTHFR中的遗传变异预测了接受5-甲化疗的结直肠癌患者的预后不佳,独立于瘤基因突变. 这些发现为治疗反应提供了潜在的生物标志物.
科学领域:
- 在瘤学瘤学.
- 药物基因组学 药物基因组学
- 癌症遗传学 癌症遗传学
背景情况:
- 结肠直肠癌 (CRC) 是一个重要的全球健康问题.
- 基于5-甲 (5FU) 的化疗方案 (例如,FOLFOX,CapeOX) 是标准的治疗方法.
- 5FU化疗反应的预测生物标志物在很大程度上仍未确立.
研究的目的:
- 研究特定遗传多态性在预测转移性CRC患者对基于5FU的化疗的治疗反应中的作用.
- 评估这些遗传变异与常见的瘤基因突变 (KRAS,NRAS,PI3KCA,AKT1,BRAF) 之间的相互作用.
主要方法:
- 对63名转移性CRC患者进行了回顾性队列研究.
- 多变量分析以确定独立的预后指标.
- 对DPYD,ABCB1和MTHFR多态的分析.
- 对瘤基因突变的评估 (KRAS,NRAS,PI3KCA,AKT1,BRAF).
- 使用药物敏感性基因组学 (GDSC) 项目的数据进行了in silico分析.
主要成果:
- 肝转移,DPYD,ABCB1和MTHFR多态性被确定为不良预后的独立指标.
- 在智利队列中,BRAF野生类型状态和高风险药物代谢多态性与不良预后相关.
- 与BRAF突变细胞系相比,GDSC数据显示BRAF野生型细胞系中的5-FU IC50值较高.
结论:
- DPYD rs1801265,ABCB1 rs1045642和MTHFR rs180113的多态可能作为预测生物标志物,用于接受5-甲化疗的患者的不良预后.
- 这些遗传标记似乎是有用的,无论同时发生的瘤基因突变.
- 需要进一步验证,以将这些发现纳入个性化CRC治疗的临床实践.
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