Analysis of immune signatures of endometrial carcinoma patients with POLE mutation
10.3969/j.issn.1000-484X.2025.04.023
- VernacularTitle:POLE基因突变型子宫内膜癌的免疫特征分析
- Author:
Yugang HUANG
1
;
Xiaomin SU
;
Li WANG
;
Xianbin TANG
Author Information
1. 十堰市太和医院/湖北医药学院附属医院病理科,十堰 442000
- Publication Type:Journal Article
- Keywords:
Endometrial carcinoma;
POLE mutation;
Analysis of immune signatures;
Bioinformatics analysis
- From:
Chinese Journal of Immunology
2025;41(4):908-914
- CountryChina
- Language:Chinese
-
Abstract:
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 ex-pressions 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 sig-nificantly 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 abun-dance of CD8+T cells and expression of PD-L1 have crucial value for prognosis or treatment of EC patients with POLE mutation.
