Zhou W, Yin M, Cui H, Wang N, Zhao L-L, Yuan L-Z, Yang X-P, Ding X-M, Men F-Z, Ma X, Na J-R
Department of Respiration, General Hospital of Ningxia Medical University, Yinchuan, China.
Eur Rev Med Pharmacol Sci. 2015 Sep;19(18):3375-84.
The study was aimed to explore the underlying mechanisms and identify the potential target genes by bioinformatics analysis for non-small-cell lung carcinoma (NSCLC) treatment in non-smoking women.
The microarray data of GSE19804 was downloaded from Gene Expression Omnibus (GEO) database. Paired samples (from the same patient) of tumor and normal lung tissues from 60 non-smoking female NSCLC patients were used to identify differentially expressed genes (DEGs). The functional enrichment analysis was performed. Furthermore, the protein-protein interaction (PPI) network of the DEGs was constructed by Cytoscape software. The module analysis was performed.
Totally, 817 DEGs including 273 up- and 544 down-regulated genes were identified. The up-regulated genes were mainly enriched in extracellular matrix (ECM)-receptor interaction, focal adhesion and cell cycle functions, while down-regulated genes were mainly enriched in the cytokine-cytokine receptor interaction pathway. DEGs including hyaluronan-mediated motility receptor (HMMR), collagen, type I alpha 2 (COL1A2), cyclin A2 (CCNA2), MAD2 mitotic arrest deficient-like 1 (MAD2L1), interleukin 6 (IL6) and interleukin 1, beta (IL1B) were identified in these functions. These genes were hub nodes in PPI networks. Besides, there were 3 up-regulated modules and 1 down-regulated module. The significant pathways were ECM-receptor interaction and focal adhesion in up-regulated modules, while in down-regulated module, the significant pathway was mitogen-activated protein kinase (MAPK) signaling pathway.
The ECM-receptor interaction, focal adhesion, cell cycle and cytokine-cytokine receptor interaction functions may be associated with NSCLC development. Genes such as HMMR, COL1A2, CCNA2, MAD2L1, IL6 and IL1B may be potential therapeutic target genes for NSCLC.
本研究旨在通过生物信息学分析探索非小细胞肺癌（NSCLC）在不吸烟女性中的潜在发病机制并确定潜在靶基因，用于NSCLC治疗。
从基因表达综合数据库（GEO）下载GSE19804的微阵列数据。使用60例不吸烟女性NSCLC患者的肿瘤和正常肺组织配对样本（来自同一患者）来鉴定差异表达基因（DEG）。进行功能富集分析。此外，通过Cytoscape软件构建DEG的蛋白质-蛋白质相互作用（PPI）网络。进行模块分析。
共鉴定出817个DEG，其中包括273个上调基因和544个下调基因。上调基因主要富集于细胞外基质（ECM）-受体相互作用、粘着斑和细胞周期功能，而下调基因主要富集于细胞因子-细胞因子受体相互作用途径。在这些功能中鉴定出包括透明质酸介导的运动受体（HMMR）、I型胶原蛋白α2（COL1A2）、细胞周期蛋白A2（CCNA2）、MAD2有丝分裂阻滞缺陷样1（MAD2L1）、白细胞介素6（IL6）和白细胞介素1β（IL1B）在内的DEG。这些基因是PPI网络中的枢纽节点。此外，有3个上调模块和1个下调模块。上调模块中的显著途径是ECM-受体相互作用和粘着斑，而下调模块中的显著途径是丝裂原活化蛋白激酶（MAPK）信号通路。
ECM-受体相互作用、粘着斑、细胞周期和细胞因子-细胞因子受体相互作用功能可能与NSCLC的发生发展相关。HMMR、COL1A2、CCNA2、MAD2L1、IL6和IL1B等基因可能是NSCLC潜在的治疗靶基因。
