通过生物信息学方法筛选肺鳞癌潜在关键基因

Identification of potential critical genes in lung squamous cell carcinoma by bioinformatic analysis

目的:通过分析肺鳞癌及癌旁组织差异表达基因,初步筛选潜在生物标志物。方法:从公共基因表达数据库(GEO)下载肺鳞癌的芯片数据集。利用R语言limma包对原始数据进行预处理并筛选差异表达基因,通过R语言的clusterProfiler包对差异表达基因进行GO和KEGG分析。利用STRING在线软件分析差异基因表达蛋白之间的相互作用,并通过Cytoscape筛选关键基因,进而用GEPIA在线软件验证关键基因的表达情况。结果:通过分析共得到734个差异表达基因,其中290个基因在肺鳞癌中上调,444个基因下调。GO分析显示差异表达基因主要参与的生物过程包括细胞外结构组织、体液水平调节、中性粒细胞介导的免疫应答等。KEGG分析显示差异表达基因主要富集在补体系统、细胞周期、DNA复制等信号通路。通过蛋白互作分析筛选出的关键基因包括PCNA、FOS、PTPRC、MMP9、CDK1、CCL2、IL6、GMPS、CCNB1、TOP2A。经验证PCNA、MMP9、CDK1、GMPS、CCNB1、TOP2A在肺鳞癌中表达增高,FOS、PTPRC、CCL2、IL6在癌组织中表达降低。结论:通过生物信息学筛选差异表达基因和信号通路可能有助于肺鳞癌的分子机制研究,筛选得到的核心基因可能成为肺鳞癌的诊断及治疗靶点。

Objective:To identify potential biomarkers by analyzing differentially expressed genes between lung squamous cell carcinoma (SCC) and para-carcinoma. Methods: SCC microarray was obtained from Gene Expression Omnibus (GEO).The original data was preprocessed,differentially expressed genes (DEGs) were identified based on limma package of R software.GO and KEGG analysis were performed by cluster Profiler of R.DEGs-associated protein-protein interaction (PPI) network was analyzed by STRING online software,and Cytoscape was used to filter the critical genes.The expression of hub genes were validated based on GEPIA. Results: 734 DEGs including 290 up-regulated genes and 444 down-regulated genes were identified from SCC GSE dataset.GO analysis results showed that DEGs were mainly enriched in extracellular structure organization,regulation of body fluid levels,neutrophil mediated immunity and other biological processes.KEGG analysis showed that DEGs were enriched in complement and coagulation cascades,cell cycle and DNA replication.Hub genes filtered from PPI network including PCNA,FOS,PTPRC,MMP9,CDK1,CCL2,IL6,GMPS,CCNB1,TOP2A.PCNA,MMP9,CDK1,GMPS,CCNB1 and TOP2A were proved to be increased in lung squamous cell carcinoma.FOS,PTPRC,CCL2 and IL6 were decreased in cancer. Conclusion: The DEGs and signal pathways obtained from bioinformatic analysis may contribute to the molecular mechanism of lung squamous cell carcinoma,the critical genes could be diagnostic markers and therapeutic targets for SCC.