Identification of Key Genes and Pathways in Gefitinib-Resistant Lung Adenocarcinoma using Bioinformatics Analysis.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2021-06-11 eCollection Date: 2021-01-01 DOI:10.1177/11769343211023767
Kailin Mao, Fang Lin, Yingai Zhang, Hailong Zhou
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引用次数: 4

Abstract

Gefitinib resistance is a serious threat in the treatment of patients with non-small cell lung cancer (NSCLC). Elucidating the underlying mechanisms and developing effective therapies to overcome gefitinib resistance is urgently needed. The differentially expressed genes (DEGs) were screened from the gene expression profile GSE122005 between gefitinib-sensitive and resistant samples. GO and KEGG analyses were performed with DAVID. The protein-protein interaction (PPI) network was established to visualize DEGs and screen hub genes. The functional roles of CCL20 in lung adenocarcinoma (LUAD) were examined using gene set enrichment analysis (GSEA). Functional analysis revealed that the DEGs were mainly concentrated in inflammatory, cell chemotaxis, and PI3K signal regulation. Ten hub genes were identified based on the PPI network. The survival analysis of the hub genes showed that CCL20 had a significant effect on the prognosis of LUAD patients. GSEA analysis showed that CCL20 high expression group was mainly enriched in cytokine-related signaling pathways. In conclusion, our analysis suggests that changes in inflammation and cytokine-related signaling pathways are closely related to gefitinib resistance in patients with lung cancer. The CCL20 gene may promote the formation of gefitinib resistance, which may serve as a new biomarker for predicting gefitinib resistance in patients with lung cancer.

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利用生物信息学分析鉴定吉非替尼耐药肺腺癌的关键基因和途径。
吉非替尼耐药性是治疗癌症(NSCLC)患者的严重威胁。迫切需要阐明其潜在机制并开发有效的疗法来克服吉非替尼耐药性。从吉非替尼敏感和耐药样品之间的基因表达谱GSE122005中筛选差异表达基因(DEG)。采用DAVID进行GO和KEGG分析。建立了蛋白质-蛋白质相互作用(PPI)网络,以可视化DEG并筛选枢纽基因。应用基因集富集分析(GSEA)检测CCL20在肺腺癌(LUAD)中的功能作用。功能分析显示,DEG主要集中在炎症、细胞趋化性和PI3K信号调节方面。基于PPI网络鉴定了10个枢纽基因。hub基因的生存分析表明,CCL20对LUAD患者的预后有显著影响。GSEA分析显示CCL20高表达组主要富集于细胞因子相关的信号通路。总之,我们的分析表明,癌症患者炎症和细胞因子相关信号通路的变化与吉非替尼耐药性密切相关。CCL20基因可能促进吉非替尼耐药性的形成,这可能作为预测癌症患者吉非替宁耐药性的新生物标志物。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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