Bu Jianlong, Zhang Pinyi, Zhu Kaibin, Yan Yubo, Shi Bowen, Wang Junfeng, Xu Shidong
Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China.
Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China.
Aging (Albany NY). 2020 Sep 14;12(18):17948-17957. doi: 10.18632/aging.103475.
This study aimed to investigate the potential pathogenesis of early non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), by constructing a global transcriptional regulatory landscape to identify hub genes and key pathways. A total of 1,206 differentially expressed genes (DEGs) in early NSCLC were identified compared to normal lung tissue samples in GSE33532 and GSE29013. DEGs-related protein-protein interaction networks (PPIs) were constructed based on the STRING database and were then modularly analyzed using the ClusterOne tool. The enrichment analysis revealed that multiple modules were significantly involved in pathways such as the TNF signaling pathway, PPAR signaling pathway and PI3K/AKt signaling pathway. Ten genes were identified as hub genes in the PPIs and also found up-regulated at protein level. The prognostic value of the hub genes and the ten hub gene set variation score varied according to the different pathological types of NSCLC, which suggested the ten hub gene expression patterns can reflect the heterogeneity of two types of NSCLC. In conclusion, by carrying out a series of in-depth analyses, hub genes and key pathways associated with early NSCLC were identified by a global transcriptional regulatory landscape.
本研究旨在通过构建全局转录调控图谱以识别枢纽基因和关键通路,从而探究早期非小细胞肺癌(NSCLC),包括肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)的潜在发病机制。与GSE33532和GSE29013中的正常肺组织样本相比,共鉴定出1206个早期NSCLC中的差异表达基因(DEG)。基于STRING数据库构建DEG相关的蛋白质-蛋白质相互作用网络(PPI),然后使用ClusterOne工具进行模块化分析。富集分析显示,多个模块显著参与肿瘤坏死因子(TNF)信号通路、过氧化物酶体增殖物激活受体(PPAR)信号通路和磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKt)信号通路等途径。在PPI中鉴定出10个基因作为枢纽基因,并且在蛋白质水平也发现它们上调。枢纽基因和十个枢纽基因集变异评分的预后价值因NSCLC的不同病理类型而异,这表明十个枢纽基因表达模式可以反映两种NSCLC的异质性。总之,通过进行一系列深入分析,利用全局转录调控图谱鉴定出了与早期NSCLC相关的枢纽基因和关键通路。