基于WGCNA联合LASSO筛选宫颈癌预后枢纽基因

Identification of Prognostic Markers in Cervical Cancer Based on WGCNA Combined with LASSO

目的运用生物信息学方法筛选宫颈癌预后相关的分子标志物,为宫颈癌的预后预测提供依据。方法从GEO、TCGA和GTEx数据库下载宫颈癌转录组表达数据和相应的临床数据。在GSE9750和GSE52903数据集中,通过WGCNA和LASSO两种方法联合筛选宫颈癌枢纽基因,GEPIA数据库进一步筛选与预后相关的枢纽基因。在GEO数据集(GSE9750和GSE52903)和TCGA联合GTEx数据集中比较预后相关的枢纽基因在宫颈癌和正常宫颈组织中的表达情况,并在HPA数据库中验证其蛋白水平的表达。利用ssGSEA分析宫颈癌肿瘤微环境(tumor microenvironment,TME)中免疫细胞浸润情况,探究预后相关的枢纽基因与免疫细胞浸润和免疫检查点基因表达的相关性。结果WGCNA和LASSO两种方法共筛选出7个宫颈癌枢纽基因,GEPIA数据库进一步筛选得到3个预后相关的枢纽基因MCM2、APOD和RAD54L。在GEO数据集(GSE9750和GSE52903)和TCGA联合GTEx数据集中,与正常宫颈组织比较,MCM2和RAD54L在宫颈癌组织中表达上调,而APOD则表达下调,与HPA数据库中免疫组化结果基本一致。3个预后相关的枢纽基因与免疫细胞和免疫检查点的表达有相关性。结论MCM2、APOD和RAD54L基因可能是与宫颈癌预后相关的分子标志物,与TME中免疫浸润相关。

Objective To screen the prognostic molecular markers of cervical cancer by bioinformatics methods,and to provide guidance for prognosis prediction of cervical cancer.Methods Cervical cancer transcriptome expression data and corresponding clinical data were acquired from Gene Expression Omnibus(GEO),the Cancer Genome Atlas(TCGA),and Genotype Tissue Expression(GTEx)databases.In the CSE9750 and GSE52903datasets,the hub genes of cervical cancer were screened by WGCNA and LASSO0.The hub genes related to prognosis were further screened by GEPIA database.The expression of prognostic-related hub genes in cervical cancer and normal cervical tissues were compared in the GEO datasets(GSE9750 and GSE52903)and TCGA combined with GTEx datasets,and the expression in protein level were verified in the HPA database.ssGSEA was used to analyze the infiltration of immune cells in the tumor microenvironment(TME)of cervical cancer,and to explore the correlation of prognostic hub genes with immune cell infiltration and immune checkpoint genes expression.Results A total of seven hub genes of cervical cancer were screened by WGCNA and LASSO,and three prognostic-related hub genes MCM2,APOD and RAD54L were further screened by GEPIA database.In the GEO datasets(GSE9750 and GSE52903),and TCGA combined with GTEx datasets,MCM2 and RAD54L were up-regulated in cervical cancer tissues compared with normal cervical tissues,while APOD was down-regulated,which was consistent with the immunohistochemical results in the HPA database.Three prognosis-related hub genes were correlated with the immune cells and immune checkpoint genes.Conclusion MCM2,APOD and RAD54L genes may be molecular markers associated with the prognosis of cervical cancer,and may be associated with immuneinfiltration inTME.