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通过生物信息学分析鉴定与肺腺癌相关的关键基因。

Identification of crucial genes associated with lung adenocarcinoma by bioinformatic analysis.

作者信息

Dai Jing-Jing, Zhou Wu-Bi, Wang Bing

机构信息

Department of Medical Laboratory, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China.

出版信息

Medicine (Baltimore). 2020 Oct 30;99(44):e23052. doi: 10.1097/MD.0000000000023052.

Abstract

Lung cancer is the world's most common malignancies and ranks first among all cancer-related deaths. Lung adenocarcinoma (LUAD) is the most frequent histological type in lung cancer. Its pathogenesis has not yet been fully elucidated, so it is of great significance to explore related genes for elucidating the molecular mechanism involved in occurrence and development of LUAD.To explore the crucial genes associated with LUAD development and progression, microarray datasets GSE7670, GSE10072, and GSE31547 were acquired from the Gene Expression Omnibus (GEO) database. R language Limma package was adopted to screen the differentially expressed genes (DEGs). The clusterProfiler package was used for enrichment analysis and annotation of the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways for DEGs. The Search Tool for the Retrieval of Interacting Genes database (STRING) was used to construct the protein interaction network for DEGs, while Cytoscape was adopted to visualize it. The functional module was screened with Cytoscape's MCODE (The Molecular Complex Detection) plugin. The crucial genes associated with LUAD were identified by cytoHubba plugin. Kaplan-Meier plotter online tool was used to perform survival analysis of the hub gene.Three hundred twenty-one DEGs in total were screened, of which 105 were upregulated and 216 were downregulated. It was found that some GO terms and pathways (e.g., collagen trimer, extracellular structure organization, heparin binding, complement and coagulation cascades, malaria, protein digestion and absorption, and PPAR signaling pathway) were considerably enriched in DEGs. UBE2C, TOP2A, RRM2, CDC20, CCNB2, KIAA0101, BUB1B, TPX2, PRC1, and CDK1 were identified as crucial genes. Survival analysis showed that the overexpression of UBE2C, TOP2A, RRM2, CDC20, CCNB2, KIAA0101, BUB1B, TPX2, and PRC1 significantly reduced the overall survival of LUAD patients. One of the crucial genes: UBE2C was validated by immunohistochemistry to be upregulated in LUAD tissues.This study screened out potential biomarkers of LUAD, providing a theoretical basis for elucidating the pathogenesis and evaluating the prognosis of LUAD.

摘要

肺癌是全球最常见的恶性肿瘤,在所有癌症相关死亡中排名第一。肺腺癌(LUAD)是肺癌中最常见的组织学类型。其发病机制尚未完全阐明,因此探索相关基因对于阐明LUAD发生发展的分子机制具有重要意义。为了探索与LUAD发生发展相关的关键基因,从基因表达综合数据库(GEO)获取了微阵列数据集GSE7670、GSE10072和GSE31547。采用R语言的Limma包筛选差异表达基因(DEG)。使用clusterProfiler包对DEG进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路的富集分析和注释。利用检索相互作用基因数据库(STRING)构建DEG的蛋白质相互作用网络,并用Cytoscape进行可视化。使用Cytoscape的MCODE(分子复合物检测)插件筛选功能模块。通过cytoHubba插件鉴定与LUAD相关的关键基因。使用Kaplan-Meier plotter在线工具对枢纽基因进行生存分析。共筛选出321个DEG,其中105个上调,216个下调。研究发现一些GO术语和通路(如胶原三聚体、细胞外结构组织、肝素结合、补体和凝血级联、疟疾、蛋白质消化和吸收以及PPAR信号通路)在DEG中显著富集。UBE2C、TOP2A、RRM2、CDC20、CCNB2、KIAA0101、BUB1B、TPX2、PRC1和CDK1被鉴定为关键基因。生存分析表明,UBE2C、TOP2A、RRM2、CDC20、CCNB2、KIAA0101、BUB1B、TPX2和PRC1的过表达显著降低了LUAD患者的总生存率。其中一个关键基因UBE2C经免疫组织化学验证在LUAD组织中上调。本研究筛选出LUAD的潜在生物标志物,为阐明LUAD的发病机制和评估预后提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f3e/7598841/497026dbed58/medi-99-e23052-g001.jpg

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