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鉴定与结直肠癌相关的枢纽基因:整合孟德尔随机化,转录组分析和实验验证

Yu Zhang^1,2, Xu Han¹, Yichun Yang¹

¹School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.

|July 29, 2025

概括

这项研究确定FUT8是结直肠癌 (CRC) 发展中的关键基因,以及它与瘤免疫力的联系. 药物VE-822通过准FUT8.8显示出治疗CRC的希望.

科学领域:

在瘤学瘤学.
遗传学是一个遗传学.
分子生物学分子生物学

背景情况:

结肠直肠癌 (CRC) 是一个重大的全球卫生挑战,死亡率高.
了解CRC的遗传基础对于推进治疗策略至关重要.

研究的目的:

使用cis-eQTL数据识别与结直肠癌 (CRC) 有因果关系的基因.
研究FUT8基因在CRC进展,瘤免疫力和治疗向中的作用.

主要方法:

利用cis-eQTL总结数据来识别潜在的CRC相关基因.
分析了瘤与正常组织 (GEPIA2) 中的FUT8表达,将其与细胞功能,瘤突变负担和免疫标记相关联.
通过MTT试验和CETSA进行了分子对接,以发现FUT8抑制剂和验证药物疗效 (VE-822).

主要成果:

确定了与CRC风险相关的19个eQTL,包括FUT8.8.
在CRC组织中FUT8过度表达与茎度,入侵,EMT,转移和较高的瘤突变负担相关.
VE-822被确定为一种针对FUT8的候选药物,抑制CRC细胞增殖并与FUT8结合.

结论:

FUT8是结直肠癌 (CRC) 发病过程中的关键基因,并影响瘤免疫力.
通过准FUT8.8,VE-822显示出作为CRC治疗剂的潜力.

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