Constructing a global transcriptional regulatory landscape for early non-small cell lung cancer to identify hub genes and key pathways.
Constructing a global transcriptional regulatory landscape for early non-small cell lung cancer to identify hub genes and key pathways.
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DOI：
10.18632/aging.103475
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发表时间：
2020-09-14
期刊：
影响因子：
--
通讯作者：
Xu S
中科院分区：
文献类型：
--
作者：
Bu J;Zhang P;Zhu K;Yan Y;Shi B;Wang J;Xu S
本研究旨在通过构建全局转录调控景观来识别中枢基因和关键通路，从而研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，在早期 NSCLC 中总共鉴定出了 1,206 个差异表达基因 (DEG)。基于STRING数据库构建DEGs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着参与TNF信号通路、PPAR信号通路、PI3K/AKt信号通路等通路。十个基因被确定为 PPI 中的中心基因，并且在蛋白质水平上也发现上调。 Hub基因和10个Hub基因集变异评分的预后价值根据NSCLC的不同病理类型而不同，这表明10个Hub基因表达模式可以反映两种类型NSCLC的异质性。总之，通过进行一系列深入分析，通过全球转录调控格局确定了与早期 NSCLC 相关的中枢基因和关键通路。
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.
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