VSIG4在乳腺癌中的表达及其与免疫浸润和预后的相关性

Expression Level of VSIG4 in Breast Cancer and Its Correlation with Immune Infiltration and Prognosis

目的分析M2型巨噬细胞在乳腺癌组织中的浸润丰度,探索VSIG4与M2型巨噬细胞的相关性及调控乳腺癌侵袭和迁移的潜在机制。方法下载TCGA-BRCA的RNA-seq数据,CIBERSORT评估样本的免疫细胞浸润丰度,构建预后风险预测模型。分析M2型巨噬细胞及VSIG4对乳腺癌患者预后的影响,基因集富集分析VSIG4参与的信号通路,并预测其上游调控miRNA。结果M2型巨噬细胞的浸润丰度与年龄、PR状态、病理分期共同参与构建风险预测模型,模型预测性能较好(AUC=0.816)。M2型巨噬细胞的高浸润(HR=1.35,P<0.05)及VSIG4的高表达(HR=1.4,P=0.039)提示乳腺癌患者预后较差。VSIG4受上游miR-29a-3p调控,与Toll样受体、细胞黏附、细胞因子的生成及释放等通路显著相关。结论VSIG4与乳腺癌患者预后及M2型巨噬细胞浸润丰度显著相关,受上游miR-29a-3p调控,VSIG4促进乳腺癌细胞的侵袭和迁移,可作为乳腺癌的潜在预后标志物。

Objective To analyze the infiltration abundance of macrophage M2 in breast cancer tissues and explore the correlation between VSIG4 and macrophage M2 and the potential mechanism of regulating the invasion and migration of breast cancer patients.Methods We downloaded the RNA-seq data of TCGA-BRCA and assessed the infiltration abundance of immune cells in the samples by CIBERSORT,and established a prognostic risk prediction model.Then,we analyzed the effect of macrophage M2 and VSIG4 on the prognosis of breast cancer patients.In addition,we analyzed the signaling pathway associated with VSIG4 by gene set enrichment analysis and predicted its upstream regulation of miRNA.Results The infiltration abundance of macrophage M2,age,PR status and pathological stage were involved in the establishment of risk prediction model,and the model had a good prediction performance(AUC=0.816).High infiltration of macrophage M2(HR=1.35,P<0.05)and high expression of VSIG4(HR=1.4,P=0.039)suggested poor prognosis of breast cancer patients.VSIG4 could be regulated by upstream miR-29a-3p and significantly correlated with Toll-like receptor,cell adhesion,production and release of cytokine.Conclusion VSIG4 is significantly associated with breast cancer patients’prognosis and infiltration of macrophage M2,regulated by the upstream miR-29a-3p and promotes the invasion and migration of breast cancer cells.It can be used as a potential prognostic marker for breast cancer.