激活ERK1/2分子通路及其与人类恶性瘤致病性的关系
A G Emelyanova1,2, M A Zolotovskaia1,2, E V Poddubskaya2
1Moscow Institute of Physics and Technology, Dolgoprudny, 141701 Russian Federation.
Acta naturae
|April 23, 2025
概括
线素激活蛋白激酶ERK1/2通路的激活在不同类型的癌症中不同影响患者的存活率. 这一发现为个性化癌症治疗策略和药物开发提供了新的生物标志物.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 线素激活蛋白激酶,ERK1/2 (MAPK3/1),是细胞生长,分化和细胞亡的关键调节者.
- 癌细胞中ERK1/2通路的激活可能导致耐药性和生长因子受体的过度表达.
- 之前的研究已经确定了ERK1/2在癌症进展和治疗耐药性方面的作用.
研究的目的:
- 用转录基因数据算法构建ERK1/2分子通路并量化它们的激活水平 (PAL).
- 调查ERK1/2 PALs对患者存活率和对各种癌症类型的向治疗的反应的影响.
- 探索ERK1/2通路激活作为预测临床结果和指导个性化治疗策略的生物标志物的潜力.
主要方法:
- 利用一种新的生物信息技术来构建基于互动原子网络的分子通路.
- 分析了来自31种癌症类型的11,287个人类瘤概况的高通量基因表达数据.
- 与患者生存数据和对29种不同的化疗和向治疗方案的反应相关的ERK1/2通路激活水平.
主要成果:
- 在不同癌症类型中,ERK1/2通路的激活显示出不同的预后意义.
- 更糟糕的生存率与质母细胞瘤,肉瘤,肺,脏,膀,胃和结肠癌中的ERK通路激活有关.
- 更好的生存率与HER2+,光线A和B乳腺癌以及子宫体癌的ERK通路激活有关.
- 对治疗反应的分析证实了生存趋势.
- 与通路激活水平相比,单个MAPK1和MAPK3基因的表达水平显示出明显较差的关联.
结论:
- ERK1/2通路激活水平作为潜在的生物标志物用于预测各种癌症患者的结果.
- ERK1/2通路激活的预后意义取决于癌症类型.
- 这些发现支持开发个性化治疗策略,包括使用MAPK抑制剂.
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