早期结直肠癌的分子异质性:高风险人群的途径特定见解
Cecilia Monge1, Brigette Waldrup2, Francisco G Carranza2
1Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Cancers
|April 26, 2025
概括
早发性结直肠癌 (EOCRC) 在西班牙裔/拉丁裔 (H/L) 患者中显示出分子差异,WNT,TGF-β和RTK/RAS通路的突变明显. 这些分子变化对种族群体的生存有不同的影响,突出了对个性化医学的需要.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 生物信息学是一种生物信息学.
背景情况:
- 早期结直肠癌 (EOCRC) 发病率正在上升,不成比例地影响西班牙裔/拉丁裔 (H/L) 人口.
- 对于EOCRC差异的分子驱动因素,特别是在致癌途径 (WNT,TGF-β,RTK/RAS) 中,尚不清楚.
- 了解这些分子差异对于开发针对高风险群体的向疗法和精准医学策略至关重要.
研究的目的:
- 识别和比较H/L和非西班牙裔白人 (NHW) 个体与EOCRC之间的WNT,TGF-β和RTK/RAS通路中的分子变化.
- 调查不同种族和年龄组在这些途径内的特定基因突变的流行情况.
- 探索这些分子差异的临床意义和预后影响.
主要方法:
- 对公共结直肠癌 (CRC) 数据集的生物信息学分析.
- 队列包括3412名患者 (302 H/L,3110 NHW),按年龄 (EOCRC <50,晚期CRC [LOCRC] ≥50) 和种族分类.
- 用千二测试比较突变频率;使用卡普兰-梅尔方法进行生存分析.
主要成果:
- 与LOCRC相比,H/L EOCRC患者显示出明显的RTK/RAS通路改变,总体频率较低,但CBL和NF1突变的患病率更高,BRAF突变更低.
- 与NHW EOCRC患者相比,H/L EOCRC患者的RNF43 (WNT),BMPR1A (TGF-beta) 和MAPK3/CBL/NF1 (RTK/RAS) 突变频率更高.
- 途径的改变没有显著影响H/L EOCRC患者的存活率,但WNT途径的改变与NHW EOCRC患者的存活率的改善相关.
结论:
- 与NHW个体相比,EOCRC表现出显著的分子异质性,特别是在H/L种群中,与NHW个体相比具有独特的遗传改变.
- 在EOCRC中,RTK/RAS路径的改变比LOCRC少.
- 调查结果强调需要对EOCRC差异进行进一步研究,并开发特定种族的精准医学方法.
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