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基于生物信息学分析鉴定非吸烟女性非小细胞肺癌中的潜在治疗靶点基因及机制

Identification of potential therapeutic target genes and mechanisms in non-small-cell lung carcinoma in non-smoking women based on bioinformatics analysis.

作者信息

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

机构信息

Department of Respiration, General Hospital of Ningxia Medical University, Yinchuan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2015 Sep;19(18):3375-84.

Abstract

OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

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。

材料与方法

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。

结果

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。

结论

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。

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