乳腺癌eIF4E对免疫细胞浸润的影响及机制的初步研究  

Preliminary study on the effect of eIF4E on immune cell infiltration and mechanism in breast cancer

作　　者：李鑫[1] 韩继媛[1] 李帆 习贵富 游思頔 张丹芳[1] LI Xin;HAN Jiyuan;LI Fan;XI Guifu;YOU Sidi;ZHANG Danfang(Department of Pathology,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]天津医科大学病理学教研室,天津300070

出　　处：《天津医科大学学报》2024年第4期295-304,共10页Journal of Tianjin Medical University

基　　金：天津市教委科研计划项目(2020KJ198)。

摘　　要：目的:研究乳腺癌真核翻译起始因子4E(eIF4E)表达对免疫细胞浸润的影响及作用机制。方法:从癌症基因组图谱(TCGA)网站获取乳腺癌数据,分析eIF4E的表达与预后和临床特征的关系。通过TISIDB数据库分析乳腺癌eIF4E表达与免疫亚型及免疫细胞浸润的关系。通过单样本基因集富集分析对免疫细胞浸润和上皮-间充质转化(EMT)抑制基因集进行评分;分析eIF4E不同表达水平时免疫细胞浸润的差异以及EMT抑制基因集和免疫细胞浸润的相关性。蛋白免疫印迹和免疫荧光实验研究乳腺癌eIF4E表达对EMT相关蛋白表达的影响,Transwell实验研究eIF4E表达对乳腺癌细胞迁移和侵袭能力的影响。结果:eIF4E在乳腺癌淋巴细胞减少型(C4)中表达最高。乳腺癌中eIF4E高表达时抗肿瘤免疫细胞浸润减少(P<0.05),免疫抑制细胞浸润增多(P<0.05);同时eIF4E表达与EMT抑制基因集评分呈负相关(P<0.05),而EMT抑制基因集评分与许多抗肿瘤免疫细胞浸润呈正相关(均P<0.05)。免疫印迹结果显示,乳腺癌eIF4E高表达时EMT相关蛋白波形蛋白(Vimentin)的表达升高(t=11.83、5.927,均P<0.05),而E-钙黏蛋白(E-cadherin)表达降低(t=2.848、8.599,均P<0.05),免疫荧光实验得到了相同的结果(t=6.577、7.843、12.48、4.406,均P<0.05)。Transwell实验显示eIF4E的高表达增强了乳腺癌细胞迁移和侵袭能力(t=13.81、8.9、15.27、4.954,均P<0.05)。结论:乳腺癌eIF4E表达通过促进EMT来影响免疫细胞的浸润。Objective:To study the effect of breast cancer eIF4E expression on immune cell infiltration and its mechanism of action.Methods:Breast cancer data were obtained from The Cancer Genome Atlas(TCGA)website to analyze the association of eIF4E expression with prognosis and clinical features.Breast cancer eIF4E expression was analyzed in relation to immune subtypes and immune cell infiltration by the TISIDB database.Immune cell infiltration and epithelial-mesenchymal transition(EMT)suppressor gene sets were scored by single-sample gene set enrichment analysis.The differences in immune cell infiltration at different expression levels of eIF4E,and the correlation between EMT suppressor gene sets and immune cell infiltration were analyzed.Protein immunoblotting and immunofluorescence experiments were performed to study the effect of eIF4E expression on EMT-related protein expression in breast cancer,and Transwell experiments were performed to study the effect of eIF4E expression on the migration and invasion ability of breast cancer cells.Results:The expression of eIF4E was highest in lymphopenic type(C4)of breast cancer.Antitumor immune cell infiltration was reduced(P<0.05)and immunosuppressive cell infiltration was increased(P<0.05)with high eIF4E expression in breast cancer.Meanwhile,eIF4E expression was negatively correlated with the EMT suppressor gene set score(P<0.05),whereas the EMT suppressor gene set score was positively correlated with the infiltration of many antitumor immune cells(all P<0.05).Immunoblotting results showed that the expression of EMT-associated protein Vimentin was increased in breast cancer with high expression of eIF4E(t=11.83,5.927,both P<0.05),whereas the expression of E-cadherin was decreased(t=2.848,8.599,both P<0.05),and immunofluorescence experiments obtained the same results(t=6.577,7.843,12.48,4.406,all P<0.05).Transwell assay showed that high expression of eIF4E enhanced breast cancer cell migration and invasion(t=13.81,8.9,15.27,4.954,all P<0.05).Conclusion:The expression of breast

关 键 词：真核翻译起始因子4E 乳腺癌 免疫细胞浸润 上皮-间充质转化 

分 类 号：R737.9[医药卫生—肿瘤]