山东大学耳鼻喉眼学报 ›› 2020, Vol. 34 ›› Issue (6): 82-91.doi: 10.6040/j.issn.1673-3770.0.2019.621
董诗坤,沈宇杰,张立庆,周涵,张佳程,董伟达
DONG Shikun, SHEN Yujie, ZHANG Liqing, ZHOU Han, ZHANG Jiacheng, DONG Weida
摘要: 目的 基于头颈部鳞癌(HNSCC)的生物标记物及其通路尚不明确的现状,研究旨在分析和鉴定HNSCC中异常甲基化的差异表达基因,探讨其关键基因和潜在通路。 方法 从GEO数据库下载基因表达的数据集GSE107591和甲基化数据集GSE33202。通过R软件筛选异常甲基化基因和差异表达基因,两者取交集后获得低甲基化高表达基因(Hypo-HGs)和高甲基化低表达基因(Hyper-LGs)。利用Enrichr对两组基因进行功能富集分析。蛋白互作(PPI)网络由STRING构建并在Cytoscape中可视化,最后利用生存分析来鉴定出关键基因。此外,还进行了免疫组化分析,利用CMap寻找可能逆转HNSCC基因表达的候选小分子。 结果 共鉴定出28个低甲基化高表达基因,GO富集分析显示其主要参与T细胞趋化性的正调节,表皮发育、细胞-基底连接组件及调节T细胞趋化性等方面。Wiki通路分析的结果表明,其主要参与典型和非典型TGF-β信号传导、血液凝结级联反应、α6β4信号通路、补体和凝血级联反应及癌症中的衰老和自噬途径。同时,发现了24个高甲基化低表达基因,主要富集于血管生成及发育的调节,对干扰素-γ反应的负调节,对干扰素-γ介导的信号通路的负调节和上皮发育的生物学过程。Wiki通路分析显示其主要参与哺乳动物含黄素单加氧酶(FMOs)的催化循环,HIF1A和PPARG调节糖酵解以及苯和黄曲霉毒素B1的代谢。此外,鉴定出与HNSCC预后相关的关键基因,分别是SERPINE1、PLAU、MMRN1、LAMB3、LAMC2、PDPN和CXCL13。 结论 通过生物信息学分析并鉴定出HNSCC中异常甲基化差异表达的基因和作用途径,为揭示HNSCC发病机制提供了重要的分子学基础。包括SERPINE1、PLAU、MMRN1、LAMB3、LAMC2、PDPN和CXCL13在内的关键基因可能作为基于甲基化的异常生物标志物,为未来寻找HNSCC诊断和治疗靶点提供了新的思路。
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