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肿瘤微环境中免疫景观对子宫内膜癌预后的意义。

Prognostic significance of immune landscape in tumour microenvironment of endometrial cancer.

机构信息

Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

J Cell Mol Med. 2020 Jul;24(14):7767-7777. doi: 10.1111/jcmm.15408. Epub 2020 May 19.

Abstract

Tumour microenvironment (TME) is crucial to tumorigenesis. This study aimed to uncover the differences in immune phenotypes of TME in endometrial cancer (EC) using Uterine Corpus Endometrial Carcinoma (UCEC) cohort and explore the prognostic significance. We employed GVSA enrichment analysis to cluster The Cancer Genome Atlas (TCGA) EC samples into immune signature cluster modelling, evaluated immune cell profiling in UCEC cohort (n = 538) and defined four immune subtypes of EC. Next, we analysed the correlation between immune subtypes and clinical data including patient prognosis. Furthermore, we analysed the expression of immunomodulators and DNA methylation modification. The profiles of immune infiltration in TCGA UCEC cohort showed significant difference among four immune subtypes of EC. Among each immune subtype, natural killer T cells (NKT), dendritic cells (DCs) and CD8 T cells were significantly associated with EC patients survival. Each immune subtype exhibited specific molecular classification, immune cell characterization and immunomodulators expression. Moreover, the expression immunomodulators were significantly related to DNA methylation level. In conclusion, the identification of immune subtypes in EC tissues could reveal unique immune microenvironments in EC and predict the prognosis of EC patients.

摘要

肿瘤微环境(TME)对于肿瘤的发生至关重要。本研究旨在通过子宫内膜癌(EC)的子宫体子宫内膜癌(UCEC)队列,揭示 TME 免疫表型的差异,并探讨其预后意义。我们采用 GVSA 富集分析将 TCGA EC 样本聚类为免疫特征聚类模型,评估 UCEC 队列(n=538)的免疫细胞谱,并定义 EC 的四种免疫亚型。接下来,我们分析了免疫亚型与包括患者预后在内的临床数据之间的相关性。此外,我们还分析了免疫调节剂的表达和 DNA 甲基化修饰。TCGA UCEC 队列的免疫浸润谱在 EC 的四种免疫亚型之间存在显著差异。在每个免疫亚型中,自然杀伤 T 细胞(NKT)、树突状细胞(DC)和 CD8 T 细胞与 EC 患者的生存显著相关。每个免疫亚型都表现出特定的分子分类、免疫细胞特征和免疫调节剂表达。此外,免疫调节剂的表达与 DNA 甲基化水平显著相关。总之,在 EC 组织中鉴定免疫亚型可以揭示 EC 中独特的免疫微环境,并预测 EC 患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675b/7348174/3b4d876db0df/JCMM-24-7767-g001.jpg

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