ABCC4基因表达对前列腺癌免疫微环境的影响

Effect of ABCC4 gene expression on immune microenvironment of prostate cancer

目的:探究ATP结合盒亚家族C成员4(ABCC4)基因在前列腺癌(PCa)中的表达,分析ABCC4对PCa肿瘤免疫微环境(TME)的影响。方法:使用GEO数据库中的GEO2R计算PCa与癌旁组织的差异表达基因。通过GEPIA2数据库探究ABCC4基因在PCa中的表达。将从UCSC Xena数据库下载的TCGA中的PCa数据分为ABCC4基因高、低表达组。使用clusterprofafiler R包进行GO分析和基因集富集分析(GSEA)。利用TISIDB数据库、ESTIMATE和CIBERSORT分析ABCC4基因表达与免疫指标的相关性。结果:PCa组织中ABCC4基因表达高于癌旁组织(P<0.05)。ABCC4高表达组PCa患者生存能力较差。在GSEA中,ABCC4低表达组中Th1和Th2细胞分化通路被激活,ABCC4基因可能在PCa的TME中起作用。TISIDB分析证实ABCC4基因表达与NK和T细胞丰度呈负相关关系(P<0.05)。ABCC4基因高表达与免疫检查点基因低表达有关。ESTIMATE和CIBERSORT分析表明,ABCC4基因表达可抑制PCa的免疫细胞浸润,尤其CD8 T、NK和Tregs细胞。免疫荧光实验显示,ABCC4蛋白表达低可诱导更多的CD8 T细胞浸润(P<0.05)。结论:ABCC4基因调控PCa的TME的免疫细胞浸润,尤其对T细胞和NK细胞浸润有重要作用,从而影响PCa的发生及其免疫治疗。

Objective:To explore the expression of ATP binding box subfamily C member 4(ABCC4)gene in prostate cancer(PCa),and to analyze the effect of ABCC4 on the tumor immune microenvironment(TME)of PCa.Methods:Differentially expressed genes between PCa and paracancerous tissues were calculated using GEO2R from GEO database.The expression of ABCC4 gene in PCa was explored by GEPIA2 database.PCa data of TCGA downloaded from UCSC Xena database were divided into high and low expression groups of ABCC4gene.GO analysis and gene set enrichment analysis(GSEA)were performed using the clusterprofafiler R package.TISIDB database,ESTIMATE and CIBERSORT were used to analyze the correlation between ABCC4 gene expression and immune indicators.Results:The ABCC4 gene expression in PCa tissues was higher than that in paracancer tissues(P<0.05).The survival ability of PCa patients with high ABCC4 expression was poor.In GSEA,Th1 and Th2 cell differentiation pathways were activated in the low ABCC4 gene expression group,which hinted that ABCC4 gene might play a role in the TME of PCa.TISIDB analysis showed that ABCC4 gene expression was negatively correlated with NK and T cell abundance(P<0.05).High expression of ABCC4 gene was associated with low expression of immune checkpoint genes.ESTIMATE and CIBERSORT analyses indicated that ABCC4 gene expression suppressed immune cell infiltration in PCa,especially CD8 T,NK,and Tregs cells.Immunofluorescence assay showed that low ABCC4 protein expression could induce more CD8 T cell infiltration(P<0.05).Conclusion:ABCC4 gene regulates the infiltration of immune cells in the TME of PCa,especially the infiltration of T cells and NK cells,thus affecting the occurrence of PCa and its immunotherapy.