基于E2F表达形状的头支状细胞癌的E2F表达形状的亚型:临床相关性,预后影响和个性化治疗
Huanyu Jiang1,2, Lijuan Zhou2, Haidong Zhang1,2
1School of Medicine, Southeast University, 87 Dingjiaqiao, Hunan Road, Nanjing, 210009, Jiangsu, China.
World journal of surgical oncology
|April 24, 2025
概括
根据E2F转录因子 (E2Fs) 确定了两种不同的头部和部状细胞癌 (HNSCC) 亚型. 这些亚型在预后,免疫透和药物敏感性方面存在差异,新的预后模型显示出强大的表现.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 头部和部状细胞癌 (HNSCC) 是一种异质的恶性瘤,预后不佳.
- E2F转录因子 (E2Fs) 的调节失调,是细胞增殖和细胞亡的关键调节者,与HNSCC的发病有关.
研究的目的:
- 通过E2F表达来探索HNSCC的分子异质性.
- 根据E2F表达式来识别不同的HNSCC亚型.
- 开发一种综合基因表达,免疫透和HNSCC药物敏感性的预后模型.
主要方法:
- 使用ConsensusClusterPlus对TCGA-HNSC数据集 (n=494) 的分析,根据八个E2F表达式对样本进行分类.
- 使用基因本体学和KEGG途径识别差异表达基因和功能丰富分析.
- 使用LASSO回归和独立数据集构建和验证七基因预后模型,并估计免疫细胞透和药物敏感性.
主要成果:
- 确定了两种不同的基于E2F的亚型:集群1 (较低的E2F) 在表皮发育和IL-17信号通路中的生存和丰富性较差,和集群2 (较高的E2F) 在DNA复制/修复通路中的生存和丰富性更好.
- 高风险患者显示M0和M2巨细胞透率增加,表明免疫抑制瘤微环境.
- 七基因预后模型表现出强的性能 (AUC 0.673-0.692,C指数 0.66) 并在高风险患者中发现对帕佐帕尼布和伊马替尼布的敏感性增加.
结论:
- 存在不同的基于E2F的HNSCC分子亚型,在预后,功能途径,免疫透和药物敏感性方面存在差异.
- 开发的预后模型为HNSCC患者提供了有价值的风险分层.
- 这些发现突出了HNSCC的潜在生物标志物和治疗目标,需要进一步验证.
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