基于生物信息学筛选与宫颈癌免疫相关的分子标志物

Screening molecular markers related to cervical cancer immunity based on bioinformatics

目的基于生物信息学方法筛选与宫颈癌免疫相关的分子标志物。方法从基因表达汇编(GEO)数据库获取24例正常宫颈组织和28例宫颈癌组织数据。从癌症基因组图谱(TCGA)数据库获取306例宫颈癌组织和3例正常宫颈组织数据。通过R软件ESTIMATE算法对数据集进行免疫、基质评分,分析评分与宫颈癌预后的关系。根据免疫评分筛选出差异表达基因(DEGs),并通过韦恩图显示其上调、下调情况,取两数据库所得交集。对关键基因进行GO富集分析、KEGG通路分析和基因集富集分析(GSEA)。构建蛋白质互作(PPI)网络。应用GEPIA2和UALCAN在线网站分析关键基因的表达水平并验证其与患者生存预后的关联性。结果基于TCGA数据库数据分析,高免疫评分组患者的生存情况优于低免疫评分组(log-rank检验:χ^(2)=4.400,P=0.035)。基于TCGA数据库数据,根据免疫评分高低进行筛选,共获得了1063个DEGs,其中包括640个上调基因和423个下调基因。基于GEO数据库数据共筛选出1903个DEGs,包括了1698个上调基因和205个下调基因。取两者交集最终得到7个下调基因和100个上调基因。针对该107个DEGs进行富集分析,GO富集分析提示DEGs参与了免疫调节的生物学功能。KEGG通路分析和GSEA结果提示DEGs主要富集于细胞因子受体的相互作用信号通路和细胞黏附分子通路。通过PPI网络进一步筛选到13个关键基因(节点数≥8),免疫细胞相关分析发现其与B细胞、T细胞等免疫细胞存在显著相关性(P<0.05)。生存分析结果显示,在这13个基因中,只有SELL和CXCL9与宫颈癌患者生存预后相关(P<0.05)。GEPIA2和UALCAN在线网站分析结果显示,CXCL9在宫颈癌组织中呈高表达(P<0.05)。但仅UALCAN的分析结果显示CXCL9高表达组的生存预后优于低表达组(P<0.05)。结论宫颈癌DEGs参与免疫调节过程。CXCL9在宫颈癌中高表达,与宫颈癌患者预后相关,有可能成为宫颈癌患者的潜在治疗靶标。

Objective To screen molecular markers related to cervical cancer immunity based on bioinformatics methods.Methods The data of 24 cases of normal cervical tissues and 28 cases of cervical cancer tissues were obtained from Gene Expression Omnibus(GEO)database and the data of 306 cases of cervical cancer tissues and 3 cases of normal cervical tissues were obtained from The Cancer Genome Atlas(TCGA)database.Immune and stroma scores were performed on the data set by ESTIMATE algorithm of R software,and the relationship between the scores and the prognosis of cervical cancer was analyzed.Differentially expressed genes(DEGs)were screened out according to the immune scores,and their up-and down-regulations were displayed by Venn diagram,and the intersection of the two databases was taken.GO enrichment analysis,KEGG pathway analysis and gene set enrichment analysis(GSEA)were performed on key genes.Protein-protein interaction(PPI)network was constructed.The expression levels of key genes were analyzed by using GEPIA2 and UALCAN online websites and their correlation with survival prognosis of the patients was verified.Results Based on the data analysis of the TCGA database,the survival of the patients in the high immune score group was better than that in the low immune score group(log-rank test:χ^(2)=4.400,P=0.035).Based on the data of the TCGA database,a total of 1063 DEGs were obtained by screening according to the level of immune score,including 640 up-regulated genes and 423 down-regulated genes.A total of 1903 DEGs were screened out based on the data of the GEO database,including 1698 up-regulated genes and 205 down-regulated genes.Finally,7 down-regulated genes and 100 up-regulated genes were obtained from the intersection of the two genes.The 107 DEGs were enriched for analysis,and GO enrichment analysis indicated that DEGs were involved in the biological function of immune regulation.KEGG pathway analysis and GSEA results indicated that DEGs were mainly enriched in cytokine receptor interaction signaling pathway and cell adhesion molecule pathway.Thirteen key genes(the number of nodes≥8)were further screened out by PPI network,and immune cell correlation analysis found that they were significantly correlated with B cells,T cells and other immune cells(P<0.05).The results of survival analysis showed that among these 13 genes,only SELL and CXCL9 were associated with the survival prognosis of cervical cancer patients(P<0.05).The analysis results of GEPIA2 and UALCAN online websites showed that CXCL9 was highly expressed in cervical cancer tissues(P<0.05).However,only the analysis results of UALCAN showed that the survival prognosis of the CXCL9 high expression group was better than that of the CXCL9 low expression group(P<0.05).Conclusion Cervical cancer DEGs are involved in the process of immune regulation.CXCL9 is highly expressed in cervical cancer and is associated with the prognosis of cervical cancer patients,and may become a potential therapeutic target for cervical cancer patients.