POLE基因突变型子宫内膜癌的免疫特征分析  

Analysis of immune signatures of endometrial carcinoma patients with POLE mutation

作　　者：黄育刚 苏小敏 王莉 汤显斌 HUANG Yugang;SU Xiaomin;WANG Li;TANG Xianbin(Department of Pathology,Taihe Hospital,Hubei University of Medicine,Shiyan 442000,China;School of Medicine,Nankai University,Tianjin 300071,China)

机构地区：[1]十堰市太和医院/湖北医药学院附属医院病理科,十堰442000 [2]南开大学医学院,天津300071

出　　处：《中国免疫学杂志》2025年第4期908-914,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金面上项目(81970488)。

摘　　要：目的:探讨POLE基因突变型子宫内膜癌(EC)的免疫特征。方法:收集2020年12月至2022年10月十堰市太和医院病理科存档的104例EC石蜡包埋组织样本,包括11例POLE突变型和93例POLE野生型。免疫组化检测EC组织中CD4、CD8、PD-L1蛋白表达;结合TCGA数据库分析POLE基因突变型的免疫浸润情况,主要包括CD4、CD8、PD-L1 mRNA的表达及相关预后分析。结果:基于TCGA数据集,与POLE野生型EC相比,POLE突变型的趋化因子家族、免疫细胞表面标志物及溶菌酶等基因的表达差异显著(均P<0.05)。POLE突变型样本中,主要富集的信号途径包括免疫调控、间质上皮转化等(均P<0.01)。相较于POLE野生型,POLE突变型EC样本中CD4^(+)T细胞、CD8^(+)T细胞、M1型巨噬细胞及树突状细胞的丰度高(均P<0.05)。TISIDB平台分析表明,POLE突变状态下,显著驱动了免疫细胞的生物学行为,包括树突状细胞、NK细胞、T细胞等免疫细胞的募集和活化、淋巴细胞归巢等。另外,POLE突变型样本中,多种免疫检查点抑制基因(包括PD-L1、CTLA-4、TIM-3等)显著高表达。临床样本也证实POLE基因突变型与CD8、CD4、PD-L1的高表达显著相关(所有P<0.001)。基于TCGA数据库的预后分析显示,CD8或PD-L1高表达且POLE突变型亚组生存期显著延长,CD8或PD-L1低表达且POLE野生型亚组生存期最短(P<0.01);而CD4亚组差异无统计学意义(P>0.05)。结论:在EC患者中,CD8^(+)T细胞浸润丰度、PD-L1表达情况对POLE突变型的预后或治疗具有重要价值。Objective:To investigate the immune signatures of endometrial carcinoma(EC)patients with POLE mutation.Methods:A total of 104 paraffin-embedded tissue samples of EC were collected from December 2020 to October 2022,including 11 POLE mutants and 93 POLE wild type in Department of Pathology,Taihe Hospital.Immunohistochemistry was conducted to detect expressions of CD4,CD8 and PD-L1 proteins in EC tissue.Combined with TCGA database,bioinformatics was used to analyze immune infiltration of POLE mutants,mainly including CD4,CD8,PD-L1 mRNA expressions and related prognosis analysis.Results:Based on TCGA database analysis,compared to POLE wild type EC,significantly different expression genes,including chemokine family,immune cell surface markers and lysozyme genes(all P<0.05),were revealed in POLE mutants.In POLE mutant samples,main enriched signaling pathways including immune regulation,mesenchymal-epithelial transformation,etc.(all P<0.01).Compared with POLE wild-type,abundance of CD4^(+)T cells,CD8^(+)T cells,M1 macrophages and dendritic cells in EC samples with POLE mutation was significantly up-regulated(P<0.05).TISIDB platform assay suggested that POLE mutants primarily drove biological behavior of immune cells,including recruitment and activation of dendritic cells,NK cells,T cells and other immune cells,and lymphocyte homing in EC.Additionally,various immunosuppressive genes(including PD-L1,CTLA-4,TIM-3,etc.)were significantly overexpressed in EC with POLE mutants.In clinical samples,it was also confirmed that POLE mutation was significantly correlated with hyper-expressions of CD8,CD4 and PD-L1(all P<0.001).Prognostic analysis of TCGA showed that survival time of CD8 or PD-L1 over-expression of the POLE mutant subgroup was significantly prolonged,while CD8 or PD-L1 down-regulation of POLE wild-type subgroup was the shortest(P<0.01);there was no significant difference in CD4 subgroup(P>0.05).Conclusion:In EC patients,infiltration abundance of CD8^(+)T cells and expression of PD-L1 have crucial value for prognosi

关 键 词：子宫内膜癌 POLE突变 免疫特征分析 生物信息学分析 

分 类 号：R711.74[医药卫生—妇产科学]