基于ceRNA网络构建和免疫细胞浸润的肾乳头状细胞癌新预后特征分析  

New prognostic features of papillary renal cell cancer based on ceRNA network construction and immune cell infiltration

作　　者：薛津 贾微微 白丽娜 牛晓辰 王晓晖[1] 王丽[1] XUE Jin;JIA Weiwei;BAI Lina;NIU Xiaochen;WANG Xiaohui;WANG Li(School of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学基础医学院病理教研室,山西太原030001

出　　处：《现代泌尿外科杂志》2022年第5期423-428,434,共7页Journal of Modern Urology

基　　金：山西省应用基础研究项目(No.201801D221262);山西省大学生创新创业训练计划项目(No.20210210)。

摘　　要：目的通过构建肾乳头状细胞癌(PRCC)相关ceRNA网络并进行分析,同时联合免疫细胞浸润,寻找新的PRCC治疗靶点和预后标志物。方法从癌症基因组图谱(TCGA)数据库下载PRCC相关基因及其临床数据,并利用R软件筛选出差异表达的RNA分子构建ceRNA网络。进行单因素Cox分析、lasso回归分析以及多因素Cox分析筛选出与预后相关的基因并构建基因风险模型。通过CIBERSORT算法对免疫细胞进行评估,去除所有表达量为0的免疫细胞并对其进行单因素Cox分析、lasso回归分析以及多因素Cox分析,筛选出与预后相关的免疫细胞构建免疫细胞风险模型。最后将基因风险模型和免疫细胞风险模型进行共表达分析。结果经过筛选后,我们发现了11个重要的基因以及2个重要的免疫细胞,分别为ELN、COL1A1、EFEMP1、SYNGR3、DBT、KCTD15、RNF149、IKBIP、ATAD5、TCF4和hsa-miR-133a-3p这11个基因,以及巨噬细胞M0和活化的CD4+记忆T细胞;共表达分析中,发现DBT与巨噬细胞M0(R=0.22,P=0.045)、TCF4与活化的CD4+记忆T细胞(R=0.37,P<0.001)呈正相关。结论筛选出的11个基因和2个免疫细胞是PRCC患者新的潜在治疗靶点以及预后标志物,共表达分析发现DBT与巨噬细胞M0、TCF4与活化的CD4+记忆T细胞呈正相关。Objective To identify new therapeutic targets and prognostic markers of papillary renal cell cancer(PRCC)by constructing a PRCC-related ceRNA network and analyzing immune cell infiltration.Methods PRCC-related genes and clinical data were downloaded from The Cancer Genome Atlas(TCGA),and differentially expressed RNA molecules were screened with R software to construct a ceRNA network.Genes associated with prognosis were screened with univariate Cox analysis,lasso regression analysis and multivariate Cox analysis to construct a gene risk model.Immune cells were evaluated with CIBERSORT algorithm and those with 0 expression level were removed.Immune cells related to prognosis were screened with univariate Cox analysis,lasso regression analysis and multivariate Cox analysis to construct an immune cell risk model.Finally,the gene risk model and immune cell risk model were used for co-expression analysis.Results Altogether 11 genes and 2 immune cells were screened,including ELN,COL1A1,EFEMP1,SYNGR3,DBT,KCTD15,RNF149,IKBIP,ATAD5,TCF4,hsa-miR-133a-3p,macrophage M0 and activated CD4+memory T cells.Co-expression analysis showed that DBT was positively correlated with macrophage M0(R=0.22,P=0.045)and TCF4 was positively correlated with activated CD4+memory T cells(R=0.37,P<0.001).Conclusion The 11 genes and 2 immune cells screened are new potential therapeutic targets and prognostic markers for patients with PRCC.DBT is positively correlated with macrophage M0,and TCF4 is positively correlated with activated CD4+memory T cells.

关 键 词：肾乳头状细胞癌 ceRNA网络 免疫细胞浸润 预后标志物 治疗靶点 基因 

分 类 号：R737.11[医药卫生—肿瘤]