早期结肠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.
medRxiv : the preprint server for health sciences
|October 1, 2025
概括
早发性结肠直肠癌 (EOCRC) 在西班牙裔/拉丁裔 (H/L) 个人中显示出患病率上升. 这项研究在H/L EOCRC患者中发现了明显的分子变化,影响了高风险人群的精准医学策略.
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:
- 早发性结直肠癌 (EOCRC) 的发病率正在增加,特别是在西班牙裔/拉丁裔 (H/L) 人群中.
- 导致EOCRC差异的分子机制及其对不同种族群体的影响尚不清楚.
- 关键的致癌途径 (WNT,TGF-β,RTK/RAS) 涉及结直肠癌 (CRC),但它们在EOCRC中的特定作用需要进一步调查.
研究的目的:
- 在H/L和非西班牙裔白人 (NHW) EOCRC患者之间识别和比较WNT,TGF-β和RTK/RAS通路中的分子变化.
- 探索这些分子差异对精准医学的临床意义.
- 为了研究EOCRC分子形状的种族变异.
主要方法:
- 对公开可用的CRC数据集进行生物信息学分析 (3,412名患者:302 H/L,3,110 NHW).
- 根据年龄 (EOCRC与晚期CRC) 和种族 (H / L与NHW) 的患者分层.
- 突变频率的统计比较和卡普兰-梅尔生存分析.
主要成果:
- 与NHW EOCRC患者相比,H/L EOCRC患者表现出明显的变化:RNF43 (WNT),BMPR1A (TGF-beta) 和CBL/NF1/MAPK3 (RTK/RAS) 突变的患病率较高.
- 在EOCRC中,RTK/RAS通路的改变在H/L个体中比晚发性CRC少.
- 在NHW EOCRC患者中,WNT通路的改变与改善的生存率有关,但在H/L EOCRC患者中并非如此.
结论:
- EOCRC表现出显著的分子异质性,特别是在高风险的H/L群体中.
- 在H/L EOCRC中明显的遗传变化强调了需要特定种族的研究和精确医学方法.
- 进一步的研究对于阐明EOCRC差异和为代表性不足的群体开发有针对性的疗法至关重要.
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