Trop-2基因在膀胱尿路上皮癌中的遗传表达和临床意义

Genetic expression and clinical significance of Trop-2 gene in bladder urothelial carcinoma

目的通过对癌症基因组图谱(TCGA)数据库中膀胱尿路上皮癌(BLCA)的数据挖掘,探讨Trop-2基因的表达及其临床意义,为Trop-2作为临床治疗靶点提供理论依据。方法利用GEPIA2、cBioPortal等在线工具分析Trop-2在泛癌中的表达情况。采用HPA数据库比较正常膀胱组织与BLCA组织Trop-2的免疫组织化学染色结果,分析其蛋白表达差异。利用R4.1.2对从TCGA数据库中提取的BLCA的基因表达信息进行富集分析,以发现潜在通路。采用共表达基因分析和肿瘤免疫浸润分析,研究Trop-2在BLCA发生中的可能作用。结果免疫组织化学染色结果证实,BLCA组织中Trop-2表达呈上调趋势,且通过参与细胞周期、p53信号通路等过程促进BLCA细胞生长、增殖和转移。肿瘤免疫浸润分析显示,Trop-2及共表达基因与B细胞呈显著正相关,而与T细胞(CD4^(+)T细胞、CD8^(+)T细胞)呈显著负相关,一定程度上说明了免疫过程在肿瘤发生中的作用。结论Trop-2在BLCA中呈高表达,同时通过多种通路和免疫过程调控肿瘤的发生,因此可能成为BLCA诊断和治疗的潜在靶点。

Objective To identify the expression and clinical significance of the Trop-2 gene through data mining of bladder urothelial carcinoma(BLCA)in The Cancer Genome Atlas(TCGA)database and discover the function of Trop-2 to provide insights into clinical therapeutic targets.Methods The gene expression of Trop-2 in pan-cancer was analyzed using online tools,GEPIA2 and cBioPortal.The immunohistochemical staining results of Trop-2 in normal bladder tissue and BLCA tissue were compared using the Human Protein Atlas(HPA)database to analyze its protein expression differences.Enrichment analysis and survival analysis were performed for all the significant genes of BLCA using R version 4.1.2.Additionally,gene co-expression analysis and immune infiltration analysis were performed to investigate the possible role of Trop-2 in the occurrence of BLCA.Results The expression of Trop-2 is upregulated in BLCA tissues,which was confirmed through immunohistochemical staining results.Its function in promoting the proliferation and metastasis of BLCA cells through participating in diverse biological processes,namely,cell cycle and p53 signaling pathway,was determined using Gene Ontology and pathway analysis.The analysis of tumor immune infiltration showed that Trop-2 and the co-expressed genes were positively associated with B cells but nega-tively associated with T cells(CD4^(+)T cells and CD8^(+)T cells).To some extent,it explains the role of immune processes in tumorigenesis.Conclusion Trop-2 was highly expressed in BLCA and helped regulate tumorigenesis through diverse pathways and immune processes.It could be a potential target for BLCA diagnosis and treatment.