Investigation of Potential Mechanisms Associated with Non-small Cell Lung Cancer
Investigation of Potential Mechanisms Associated with Non-small Cell Lung Cancer
复制标题
与非小细胞肺癌相关的潜在机制的研究
DOI：
10.1089/cmb.2019.0081
复制
发表时间：
2020-02-12
影响因子：
1.7
通讯作者：
Yao, Ninghua
中科院分区：
文献类型：
--
作者：
Shi, Yu;Zhu, Shan;Yao, Ninghua
本研究旨在探讨非小细胞肺癌（NSCLC）的关键机制。NSCLC相关微阵列数据GSE 27262从Gene Expression Omnibus下载，包括7份NSCLC 1a样本，18份NSCLC 1b样本及其匹配的正常样本。通过蛋白质相互作用（PPI）网络构建、功能富集分析和加权基因共表达网络分析（WGCNA），确定NSCLC 1a和NSCLC 1b样本之间的共同差异表达基因（DEG）。此外，基于来自癌症基因组图谱（TCGA）数据库的肺腺癌（LUAD）数据确认关键DEG，随后进行临床预后分析。确定了802例（NSCLC 1a）和734例（NSCLC 1b）DEG。通过交叉分析，我们获得了255个上调和97个下调的共同DEG。上调的DEG在质膜和细胞外区域显著富集，而下调的DEG在细胞骨架和细胞周期过程中显著富集。拓扑异构酶（DNA）II α（TOP 2A）和细胞周期蛋白B1（CCNB 1）是PPI网络中的枢纽节点。在WGCNA的基础上，得到了5个模块。在MEgreen模块中，DEG显著富集于精氨酸-细胞因子受体相互作用和粘着斑。值得注意的是，基于TCGA数据库的LUAD数据识别了1797个DEG;其中，285个DEG是从GSE 27262数据识别的常见DEG。TOP 2A和CCNB 1的上调与患者的不良生存相关。本研究中发现的枢纽基因和关键通路有助于全面了解NSCLC的分子机制。
This study aimed at investigating the crucial mechanisms underlying non-small cell lung cancer (NSCLC). NSCLC-related microarray data GSE27262 were downloaded from Gene Expression Omnibus, including 7 NSCLC 1a samples, 18 NSCLC 1b samples, and their matched normal samples. The common differentially expressed genes (DEGs) between NSCLC 1a and NSCLC 1b samples were identified, followed by protein-protein interaction (PPI) network construction, functional enrichment analysis, and weighted gene co-expression network analysis (WGCNA). Further, the key DEGs were confirmed based on the lung adenocarcinoma (LUAD) data from the Cancer Genome Atlas (TCGA) database, followed by clinical prognostic analysis. There were 802 (NSCLC 1a) and 734 (NSCLC 1b) DEGs identified. By intersection analysis, we obtained 255 upregulated and 97 downregulated common DEGs. Upregulated DEGs were significantly enriched in the plasma membrane and extracellular region, whereas the downregulated DEGs were significantly enriched in the cytoskeleton and cell cycle process. Topoisomerase (DNA) II alpha (TOP2A) and cyclin B1 (CCNB1) were hub nodes in the PPI network. Based on WGCNA, 5 modules were obtained. In the module MEgreen, DEGs were significantly enriched in cytokine-cytokine receptor interaction and focal adhesion. Notably, 1797 DEGs were identified based on the LUAD data from the TCGA database; among them, 285 DEGs were common DEGs identified from GSE27262 data. Upregulation of TOP2A and CCNB1 was correlated with poor survival of patients. The hub genes and key pathways identified in this study are helpful for a comprehensive knowledge of the molecular mechanisms of NSCLC.