基于TCGA数据库筛选胆管癌肿瘤微环境相关的预后基因

Screening of prognostic genes in the cholangiocarcinoma tumor microenvironment based on TCGA database

目的:运用ESTIMATE肿瘤微环境评分算法,从来自TCGA数据库的胆管癌数据中筛选与肿瘤微环境相关的基因,并利用生物信息学方法分析所得基因在胆管癌中的预后意义。方法:从TCGA数据库中获得45个胆管癌基因表达数据,利用ESTIMATE肿瘤微环境评分算法对其进行评分后,分为高分/低分组,分别筛选差异表达基因后,取交集获取共表达基因。利用DAVID在线分析工具根据对共表达基因进行GO功能富集分析和KEGG通路富集分析。利用来自TCGA数据库中的胆管癌生存数据对共表达基因进行Kaplan-Meier生存分析,筛选后获得预后基因。结合STRING网站中对差异表达基因构建的蛋白互作网络(protein-protein interaction,PPI),得到网络枢纽基因后使用其他生物学分析工具验证。结果:在45例胆管癌样本中分析筛选出11个与肿瘤微环境相关的预后基因,这些基因表达的上调对胆管癌的不良预后具有显著意义(P<0.05)。通过蛋白互作网络分析和其他生物学工具分析获得VAV1基因,该基因在免疫调控、细胞凋亡、RET信号通路调控等方面有重要作用。结论:从本研究中筛选出的VAV1基因可作为胆管癌的分子标志物,为胆管癌的诊断、免疫治疗靶点及预后提供参考。

Objective:To screen differentially expressed genes related to tumor microenvironment from the TCGA database with the ESTIMATE algorithm in cholangiocarcinoma,to identifi the molecular markers for cholangiocarcinoma by bioinformatic analysis.Methods:45 gene expression profiles of cholangiocarcinoma samples were obtained from the TCGA database.The data was assessed by ESTIMATE algorithm and divided into high and low groups by the scores.Limma was used to extract differentially expressed genes,and co-expressed genes were obtained by Venn diagram.GO enrichment analysis and KEGG pathway analysis were performed with DAVID tool.The prognosis of co-expressed genes was analyzed combined with the curated survival data of cholangiocarcinoma from TCGA database,11 prognostic genes were obtained after Kaplan-Meier survival analysis.The protein-protein interaction(PPI)network of co-expressed genes was constructed to screen hub genes by using STRING,and other biological analysis tools was used to validated the expression of hub genes in cholangiocarcinoma.Results:11 prognostic genes related to tumor microenvironment were analyzed and screened from 45 cholangiocarcinoma samples.The up regulation of these genes was significantly associated with the poor prognosis of cholangiocarcinoma(P<0.05).VAV1 gene was identified as a key target in immune response,cell apoptosis and RET signaling,was obtained by PPI network analysis and other biological tools.Conclusion:VAV1 gene is identified from this study and can be used as a molecular marker of cholangiocarcinoma,providing reference for the diagnosis,targeted immunotherapy,and prognosis of cholangiocarcinoma.