【摘要】 目的：研究乳腺癌真核翻译起始因子4E(e IF4E)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e IF4E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e IF4E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e IF4E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e IF4E表达对EMT相关蛋白表达的影响，Transwell实验研究e IF4E表达对乳腺癌细胞迁移和侵袭能力的影响。结果：e IF4E在乳腺癌淋巴细胞减少型（C4）中表达最高。乳腺癌中e IF4E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e IF4E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e IF4E表达通过促进EMT来影响免疫细胞的浸润。更多还原

【Abstract】 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 e IF4E,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 e IF4E expression in breast cancer.Meanwhile,e IF4E 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(allP<0.05).Immunoblotting results showed that the expression of EMT-associated protein Vimentin was increased in breast cancer with high expression of e IF4E(t=11.83,5.927,bothP<0.05),whereas the expression of E-cadherin was decreased(t=2.848,8.599,bothP<0.05),and immunofluorescence experiments obtained the same results(t=6.577,7.843,12.48,4.406,allP<0.05). Transwell assay showed that high expression of e IF4E enhanced breast cancer cell migration and invasion(t=13.81,8.9,15.27,4.954,allP<0.05).Conclusion:The expression of breast cancer eIF4E influences immune cell infiltration by promoting EMT.更多还原