基于公共数据库通过生物信息学分析鉴定结肠腺癌中的枢纽基因和功能模块。
Identification of hub genes and functional modules in colon adenocarcinoma based on public databases by bioinformatics analysis.
作者信息
Zhang Zhipeng, Luo Aihong, Zeng Zhijun, Zhou Yikai, Wu Wei
机构信息
Department of Geratology Surgery, Xiangya Hospital, Central South University, Changsha, China.
Teaching and Research Section of Clinical Nursing, Xiangya Hospital, Central South University, Changsha, China.
出版信息
J Gastrointest Oncol. 2021 Aug;12(4):1613-1624. doi: 10.21037/jgo-21-415.
BACKGROUND
Colon adenocarcinoma (COAD) is one of the most common cancers in the world. Although an extensive effort has been made to elucidate its pathogenesis, the underlying molecular mechanisms and genetic characteristics remain elusive.
METHODS
In this study, protein-coding transcript expression profiles of COAD were downloaded from the Cancer RNA-Seq Nexus (CRN) database. They were then integrated to identify the overlapping transcripts expressed in every COAD RNA sequencing (RNA-seq) subset. The functional annotation of these overlapping genes (OLGs) involved noting their biological process (BP), cellular components (CC), molecular function (MF) for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway in the Database for Annotation, Visualization and Integrated Discovery (DAVID). Protein-protein interaction (PPI) networks were then constructed and analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape 3.8.2.
RESULTS
A total of 10 hub genes and 3 functional modules were screened by the plugin cytoHubba and MCODE, respectively. The plugin ClueGO and DAVID were used for the functional enrichment analyses of both hub genes and modules. The expression of hub genes was verified through the gene expression profiling interactive analysis (GEPIA) database. Survival analysis of the hub genes revealed that low expressions of , , and were significantly associated with an improved COAD prognosis. Furthermore, the expression level of in stages I/II was lower than that in stages III/IV, which seems to explain why the low expression of results in a better prognosis.
CONCLUSIONS
The identification of hub genes, functional modules, and pathways have the potential to improve our understanding of the causes and underlying molecular events of COAD. The hub gene could also be a prognostic monitoring indicator or therapeutic target in the treatment of COAD.
背景
结肠腺癌（COAD）是世界上最常见的癌症之一。尽管人们为阐明其发病机制付出了巨大努力，但其潜在的分子机制和遗传特征仍不清楚。
方法
在本研究中，从癌症RNA测序中心（CRN）数据库下载了COAD的蛋白质编码转录本表达谱。然后将它们整合，以识别在每个COAD RNA测序（RNA-seq）子集中表达的重叠转录本。这些重叠基因（OLGs）的功能注释包括在注释、可视化和综合发现数据库（DAVID）中记录它们的生物学过程（BP）、细胞成分（CC）、分子功能（MF），用于基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路。然后使用检索相互作用基因/蛋白质的搜索工具（STRING）和Cytoscape 3.8.2构建并分析蛋白质-蛋白质相互作用（PPI）网络。
结果
分别通过插件cytoHubba和MCODE筛选出10个枢纽基因和3个功能模块。使用插件ClueGO和DAVID对枢纽基因和模块进行功能富集分析。通过基因表达谱交互式分析（GEPIA）数据库验证了枢纽基因的表达。对枢纽基因的生存分析表明，[具体基因名称1]、[具体基因名称2]和[具体基因名称3]的低表达与COAD预后改善显著相关。此外，[具体基因名称4]在I/II期的表达水平低于III/IV期，这似乎解释了为什么[具体基因名称4]的低表达会导致更好的预后。
结论
枢纽基因、功能模块和通路的鉴定有可能增进我们对COAD病因和潜在分子事件的理解。枢纽基因[具体基因名称4]也可能是COAD治疗中的预后监测指标或治疗靶点。
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