解读替代拼接事件及其对结直肠癌的治疗影响
Wenbo Ding1, Qianni Xiao1, Yanzhe Yue1
1General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; School of Basic Medicine and Clinical Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, China.
Cellular signalling
|March 14, 2024
概括
替代拼接 (AS) 事件在结直肠癌 (CRC) 中发生显著变化,可以将瘤与正常组织区分开来. 特定的AS事件也预测了CRC患者的预后,突出了它们在癌症进展中的作用.
科学领域:
- 分子生物学分子生物学
- 癌症基因组学 癌症基因组学
- 生物信息学是一种生物信息学.
背景情况:
- 大肠直肠癌 (CRC) 是一种普遍存在的恶性瘤,具有复杂的分子基础.
- 替代拼接 (AS) 是一个关键的基因表达调节器,与CRC发育有关.
- 了解CRC中的AS对于识别诊断和预后生物标志物至关重要.
研究的目的:
- 为了确定CRC和正常组织之间的差异性AS事件.
- 开发基于AS事件的CRC预后预测模型.
- 研究PRMT5-PCBP1在CRC相关的AS中的调控作用.
主要方法:
- 来自TCGA SpliceSeq数据库的AS百分比分离 (PSI) 值的分析.
- 机器学习算法 (Lasso,SVM) 用于特征选择.
- 统变COX回归,卡普兰-梅尔和决策曲线分析用于预后建模.
- 使用免疫沉和PCR进行实验验证.
主要成果:
- 五个AS事件,包括HNF4A变异,有效地区分了CRC与正常组织.
- 一个包含21个AS事件的机器学习模型准确预测了CRC预后.
- 通过模型识别的高风险患者的存活时间显著缩短.
- 表明PRMT5可以调节PCBP1,影响OBSCN AS,并可能导致CRC的进展.
结论:
- 特定的AS事件在CRC中显著改变,并作为潜在的诊断标记.
- AS事件与CRC预后有关,使得预测模型的开发成为可能.
- 在CRC特异性AS事件和癌症进展中,PRMT家族介导的阿基宁修饰是至关重要的.
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