基于GEO数据库探讨与马兜铃酸暴露相关的上尿路尿路上皮癌免疫浸润的生物信息学分析

Bioinformatic analysis of immune infiltration of upper urinary tract urothelial carcinoma associated with aristolochic acid exposure based on GEO database

目的探讨与马兜铃酸暴露相关的上尿路尿路上皮癌(UTUC)组织中免疫细胞浸润的类型,分析其与肿瘤临床特征之间的关系。方法从基因表达综合(GEO)数据库中下载UTUC患者的基因芯片表达谱数据并对免疫细胞样本数据进行校正,然后通过CIBOSORT反卷积算法计算22种免疫细胞在UTUC组织和正常尿路上皮组织中的浸润情况,确定相关免疫细胞的比例。通过R软件绘制的各类图谱分析肿瘤组织细胞和正常组织细胞的结果,比较肿瘤组织细胞和正常组织细胞之间免疫细胞浸润的差异。结果UTUC组织的免疫细胞浸润中,滤泡辅助性T细胞、调节性T细胞、M0巨噬细胞、M1巨噬细胞和活化的树突状细胞浸润的丰富度要明显高于正常尿路上皮组织(P<0.05)。结论UTUC组织中免疫细胞浸润的类型区别于正常上尿路尿路上皮组织,提示肿瘤免疫微环境可能参与了UTUC的发生、发展,可作为药物靶向治疗的辅助指标。

Objective To investigate the type of immune cell infiltration in upper urinary tract urothelial carcinoma(UTUC)tissue associated with aristolochic acid exposure and to analyze the relationship between it and the clinical features of the tumor.Methods The gene microarray expression profile data of UTUC patients were downloaded from the Gene Expression Omnibus(GEO)database and the immune cell sample data were corrected,and then the percentage of relevant immune cells was determined by calculating the infiltration of twenty-two immune cells in UTUC tissue and normal urothelial tissue by the CIBOSORT deconvolution algorithm.The results of tumor tissue cells and normal tissue cells were analyzed by various types of mapping drawn by R software to find differences in immune cell infiltration between UTUC tissue cells and normal tissue cells.Results Among the infiltrating immune cells in UTUC tissue,the infiltration abundance of follicular helper T cells,regulatory T cells,M0 macrophages,M1 macrophages,and activated dendritic cells was significantly higher that in normal urothelial tissue(P<0.05).Conclusions The type of immune cell infiltration in UTUC tissues differed from normal upper urinary tract urothelial tissues,suggesting that the immune cell microenvironment may be involved in the occurrence and development of UTUC,which can be used as an auxiliary indicator for drug-targeted therapy.