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.
Highlights
Cancer remains one of the leading diseases with high mortality worldwide
Kaplan-Meier curve analysis of immune subtypes showed that natural killer T cells (NKT), dendritic cells (DCs), CD8+T cells, basophils were significantly associated with OS in endometrial cancer (EC) patients (Figure 3B)
Molecular classification theory based on sequencing analysis has compensated for the limitations of traditional classification to some extent, which categorizes EC into four types, including POLE hypermutation, microsatellite instability, endometrial-like low copy number and serous high copy number
Summary
Cancer remains one of the leading diseases with high mortality worldwide. Genetic mechanisms are crucially implied in cancer initiation, progression and metastasis. The Cancer Genome Atlas (TCGA) have become valuable resources of genetic data on a wide variety of tumours in human.[1,2] TCGA provide systematic information on DNA mutation, methylation, RNA expression and other comprehensive datasets on primary cancer tissues.[3]. Recent studies have shown that immunosuppressive microenvironment, including but not limited to tumour-infiltrating lymphocytes (TILs), regulatory T cells (Treg), tumour-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), could predict worse outcomes in solid tumours such as melanoma, breast, lung, ovarian, bladder, prostate and renal cancer.[4] complex interaction between host immunity and solid tumour remains to be completely explored. Characterization of immune microenvironment based on gene expression signatures, immune subtypes, immunomodulators
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