子宫内膜癌肿瘤微环境中预后相关基因的生物信息学分析及表达谱分析

Bioinformatics analysis and expression profile analysis of prognostic related genes in the tumor microenvironment of endometrial carcinoma

目的:结合生物信息学分析和PCR表达验证,探索子宫内膜癌(endometrial carcinoma,EC)肿瘤微环境中的预后关键基因。方法:下载获取TCGA数据库中552例EC患者的基因表达数据,应用R软件ESTIMATE算法进行免疫评分和基质评分,筛选表达差异基因。多种算法对差异基因的预后情况和相关通路进一步探索。PCR实验分析差异基因在细胞系中的表达相关性。结果:Cox回归分析和KM生存分析提示CCR4(C-C motif chemokine receptor 4,CCR4)为潜在预后相关基因。GSEA(gene set enrichment analysis,GSEA)、KEGG(kyoto encyclopedia of genes and genomes,KEGG)分析结果发现,CCR4在免疫应答-激活细胞表面受体信号通路中显著富集。RT-qPCR结果表明,在细胞水平,CCR4在肿瘤组的表达显著高于非肿瘤组。结论:子宫内膜癌的肿瘤微环境中存在免疫浸润,CCR4有望成为新的子宫内膜癌诊断标记物。

Objective:To explore the key prognostic genes in the tumor microenvironment of endometrial carcinoma by bioinformatics analysis and PCR expression verification.Methods:The gene expression data of 552 patients with endometrial carcinoma were downloaded from TCGA database,and the immune score and interstitial score were performed by R software ESTIMATE algorithm to screen the differentially expressed genes.A variety of algorithms were used to further explore the prognosis of differential genes and related pathways.PCR assay was used to analyze the expression correlation of differential genes in clinical tissues and cell lines.Results:Cox regression analysis and KM survival analysis indicated that CCR4 was a potential prognostic gene.GSEA and KEGG results showed that CCR4 was significantly enriched in the immune response-activation cell surface receptor signaling pathway.The results of RT-qPCR showed that the expression of CCR4 in tumor group was significantly higher than that in non-tumor group at cell level and tissue level.Conclusion:Immunoinfiltration exists in the tumor microenvironment of endometrial carcinoma,and CCR4 is expected to be a new diagnostic marker for endometrial carcinoma.