基于生物信息学分析宫颈鳞癌的关键基因与免疫细胞浸润

Bioinformatics analysis of key genes and immune cell infiltration in cervical squamous cell carcinoma

目的:利用数据库芯片信息探寻宫颈鳞癌致病的关键基因,并从免疫细胞浸润角度探讨其可能作用机制。方法:从高通量基因表达(GEO)数据库获取基因芯片GSE63514,运用R语言“limma”等相关拓展包筛选差异表达基因,利用R语言“cluster Profiler”等拓展包进行基因本体(GO)功能富集分析、京都基因与基因组百科全书(KEGG)通路富集分析,通过String和Cytoscape软件构建蛋白质相互作用网络图,并筛选出关键基因。采用癌症基因组图谱(TCGA)数据库获取宫颈鳞癌基因表达谱验证hub基因。使用随机森林算法筛选疾病关键基因,然后基于CIBERSORT反卷积算法对免疫细胞浸润模式进行分析。结果:共筛选出569个差异表达基因,其中上调262个,下调307个。GO分析显示,宫颈鳞癌主要与细胞周期、有丝分裂高度相关;KEGG分析显示,宫颈鳞癌主要与细胞周期过程、驱动蛋白高度相关。基于hub基因的随机森林算法筛选出TTK、CDK1、KIF23、KIF2C、NUSAP1共5个关键基因。免疫浸润模式分析结果显示,幼稚CD4^(+)T细胞在宫颈鳞癌中表达显著上调。结论:TTK、CDK1、KIF23、KIF2C、NUSAP1基因与宫颈鳞癌发生发展密切相关,幼稚CD4^(+)T细胞等免疫细胞在宫颈鳞癌的发生发展中具有重要作用。

OBJECTIVE:To use chip data of datasets to identify key pathogenic genes for cervical squamous cell carcinoma,and to investigate mechanisms of action regarding the level of immune cell infiltration.METHODS:The GSE63514 dataset was downloaded from the GEO database.Using the dataset and the limma package in R language,d differentially expressed genes of cervical squamous cell carcinoma.The clusterProfiler package in R language was used to conduct functional enrichment analysis(GO term and KEGG pathway).Then,Protein interaction network maps were constructed,and key genes were screened by using the String and Cytoscape software.The Cancer Genome Atlas(TCGA)database was used to obtain the gene expression profile of cervical squamous cell carcinoma for identification of hub genes.Disease-critical genes were screened using the random forest analysis,followed by the analysis of immune cell infiltration patterns based on the CIBERSORT deconvolution algorithm.RESULTS:569 differentially expressed genes were identified,of which 262 were up-regulated and 307 were down-regulated.The GO analysis showed that the carcinomas were mainly involved with cell cycle process and mitosis.The KEGG analysis showed that the carcinomas were mainly highly correlated with cell cycle and motor proteins.The random forest analysis based on hub genes screened:5 key genes:TTK,CDK1,KIF23,KIF2C,NUSAP1.The results of immune infiltration showed that in naïve CD4^(+)T cell expression was significantly upregulated in the carcinomas.CONCLUSION:The genes TTK,CDK1,KIF23,KIF2C and NUSAP1 were closely related to the development of cervical squamous cell carcinoma,and immune cells such as naive CD4^(+)T cells had an important role in the development of the carcinomas.