利用生物信息学分析鉴定鼻咽癌转移的信号通路及核心基因

Identification of signaling pathways and core genes in nasopharyngeal carcinoma metastases using bioinformatics analysis

目的利用基因芯片技术和生物信息学分析方法,筛选出鼻咽癌转移相关的核心基因和相关信号通路,为寻找鼻咽癌转移早期诊断和靶向治疗潜在标志物提供依据。方法GSE103611的表达芯片从Gene Expression Omnibus(GEO)数据库中下载,该数据库中包含48个样本,包括24个原发鼻咽癌样本和24个放疗后转移的鼻咽癌样本。整理微阵列数据集获得差异表达基因(DEGs)与本课题组前期构建的相对于CNE-2侵袭转移能力更强的CNE-2SI细胞对比芯片差异基因进行比对获得共同差异基因。利用基因本体论(GO)和京都百科全书基因和基因组数据库(KEGG)对共同差异基因进行富集并利用DAVIDE在线进行分析。共同差异基因的蛋白质互作(PPI)网络由STRING数据库构建。Hub基因分析通过Cytoscape软件中的cytoHubba插件制作。关键基因的生存分析通过Kaplan Meier-plotter数据库分析获得。结果GSE103611数据集中共鉴定出差异基因共3301个,其中上调506个,2795个基因被下调。本课题组的芯片中差异基因共2691个,其中上调1349个,1342个基因被下调。两个芯片共同上调基因47个,下调基因135个,共计182个。GO分析表明共同差异基因的生物学功能主要集中在基本的生物学过程和细胞黏附;主要的细胞成分包括细胞膜和细胞质;分子功能包括ATP结合等(P<0.05)。KEGG通路分析显示这些共同差异基因主要参与脂类代谢、MAPK信号通路和细胞黏附信号通路(P<0.05)。CytoHubba插件分析从PPI网络中找到前20个具有高度关联性的核心基因。生存分析发现CXCL10、CUL7、PLCB2可能与在鼻咽癌不良预后相关(P<0.05)。结论利用生物信息学分析筛查鼻咽癌转移相关DEGs和通路可以帮助了解鼻咽癌转移发生的分子机制,对鼻咽癌转移的早期诊断具有临床意义。

Objective To provide a basis for the early diagnosis and targeted therapy potential markers of NPC metastasis,the core genes and related signal pathways related to NPC metastasis were screened out using gene chip technology and bioinformatics analysis method.Methods The expression profile of GSE103611 was downloaded from the Gene Expression Omnibus(GEO)database,which contained 48 samples including 24 NPC primary tumor samples and 24 NPC metastatic tumor samples.Microarray datasets were sequenced to obtain differentially expressed genes(DGEs).Common differentially expressed genes were obtained by comparison with the differentially expressed genes in contrast chips of the CNE-2SI cells constructed by our research group in the earlier stage,which were more capable of invasion and metastasis than CNE2.Gene ontology and DGEs enrichment of the Kyoto Encyclopedia Gene and Genome(KEGG)pathway were performed by DAVID online analysis.DGE’s protein-protein interaction(PPI)network was constructed from the STRING database.Hub gene analysis was made using the cytoHubba plugin in Cytoscape software.Survival analysis of key genes was obtain via Kaplan Meier-plotter database.Results A total of 3301 differential genes were identified in the GSE103611,of which 506 genes were up-regulated and 2795 genes were down-regulated.There were 2691 differential expressed genes in our microarray,of which 1349 genes were up-regulated and 1342 genes were down-regulated.47 up-regulated and 135 down-regulated common DEGs were identified,respectively.GO analysis indicated that the biological function of total 182 common DGEs were mainly concentrated in basic biological process and cell adhesion.The main cellular components include plasma membrane part and cytosol.Molecular functions included ATP binding.KEGG pathway analysis revealed that these DGEs were mainly involved in the glycerolipid metabolism signaling pathway,MAPK signaling pathway and cell adhesion molecules(CAMs)signaling pathway.Top 20 hub gene were screened out by cytoHubba plugin in Cytoscape software.Among the top 20 hub genes,3 down-regulated hub genes(CXCL10,CUL7,PLCB2)had significant prognostic values in head and neck squamous cell carcinoma.Conclusion Bioinformatics analysis of DEGs and pathways related to nasopharyngeal carcinoma metastasis can help to understand the molecular mechanism of nasopharyngeal carcinoma metastasis,which has clinical significance for the early diagnosis of nasopharyngeal carcinoma metastasis.