基于生物信息学方法分析R-spondin3在乳腺癌中的表达及其预后价值

Expression of R-spondin3 in Breast Cancer and its Prognostic Value Based on Bioinformatics Analysis

目的探讨R-spondin3(RSPO3)在乳腺癌中的表达及预后价值。方法应用TIMER、癌症基因组图谱(The Cancer Genome Atlas,TCGA)、基因表达谱数据动态分析(gene expression profilling in-teractive analysis 2,GEPIA2)、人类蛋白质表达图谱(Human Protein Atlas,HPA)等数据库分析RSPO3在乳腺癌组织和癌周正常组织中的差异表达,并分析其表达水平与乳腺癌病理学参数之间的相关性;GEPIA2数据库探讨RSPO3转录本在乳腺癌中的表达及其结构特征;Kaplan-Meier Plotter绘制RSPO3与乳腺癌患者的预后生存曲线;运用基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)等对其进行基因功能富集分析和代谢通路分析;应用TIMER数据库分析RSPO3的表达水平与肿瘤微环境中免疫细胞浸润的相关性。结果RSPO3在乳腺癌中呈低表达,且其表达水平与乳腺癌患者的年龄、肿瘤最大径、分子分型相关,在乳腺癌中低表达的RSPO3与患者的预后不良相关;GO功能富集分析显示,RSPO3相互作用的基因主要富集于免疫细胞及其受体等参与的生物学过程;免疫细胞浸润分析结果显示,RSPO3在乳腺癌组织中的表达水平与CD8^(+)T细胞、CD4^(+)T细胞、CD4^(+)记忆T细胞、巨噬细胞、B细胞等的浸润水平呈正相关,而与调节性T细胞(Treg细胞)的浸润水平呈负相关;KEGG代谢通路分析显示,RSPO3可能参与Wnt/β-catenin通路。结论在乳腺癌中低表达的RSPO3与患者的不良预后相关,其可能通过抑制免疫细胞浸润及活化Wnt/β-catenin通路参与乳腺癌的进展。

Objective To investigate the expression of R-spondin3(RSPO3)in breast cancer and its prognostic value.Methods TIMER,The Cancer Genome Atlas(TCGA),Gene ExpressionProfilling In-teractive Analysis 2(GEPIA2),Human Protein Atlas(HPA)and other databases were used to analyze the differential expression of RSPO3 in breast cancer tissues and normal tissues around cancer,and analyze the correlation between its expression level and pathological parameters of breast cancer;then the expression and structural characteristics of RSPO3 transcripts in breast cancer were investigated by GEPIA2database;Kaplan-Meier Plotter was used to plot the prognosis survival curve between RSPO3 and breast cancer patients;gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)were used for gene function enrichment analysis and metabolic pathway analysis;TIMER database was used to analyzed the relationship between RSPO3 expression level and immune cell infiltration in tumor microenvironment.Results RSPO3 was low expressed in breast cancer,and its expression level was related to the age,tumor diameter and molecular type of breast cancer patients.The low expression of RSPO3 in breast cancer was related to poor prognosis of patients;the results of GO function enrichment analysis showed that RSPO3 interacting genes were mainly enriched in biological processes involving immune cells and their receptors;the results of immune cell infiltration analysis showed that the expression level of RSPO3 in breast cancer tissue was positively correlated with the infiltration level of CD8^(+)T cells,CD4^(+)T cells,CD4^(+)T cell memory,macrophages,B cells,etc.It was negatively correlated with the infiltration level of Treg;the results of KEGG metabolic pathway analysis showed that RSPO3may be involved in Wnt/β-catenin pathway.Conclusion Low expression of RSPO3 in breast cancer is related to the poor prognosis of patients,which may be involved in the progression of breast cancer through inhibition of immune cell infiltration and activation of Wnt/β-catenin pathway.