Abstract
BackgroundEndometrioid endometrial adenocarcinoma (EEA) is one of the most common tumors in the female reproductive system. With the further understanding of immune regulation mechanism in tumor microenvironment, immunotherapy is emerging in tumor treatment. However, there are few systematic studies on EEA immune infiltration.MethodsIn this study, prognostic tumor-infiltrating immune cells (TIICs) and related genes of EEA were comprehensively analyzed for the first time through the bioinformatics method with CIBERSORT algorithm as the core. Gene expression profile data were downloaded from the TCGA database, and the abundance ratio of TIICs was obtained. Kaplan–Meier analysis and Cox regression analysis were used to identify prognostic TIICs. EEA samples were grouped according to the risk score in Cox regression model. Differential analysis and functional enrichment analyses were performed on high- and low-risk groups to find survival-related hub genes, which were verified by Tumor Immune Estimation Resource (TIMER).ResultFour TIICs including memory CD4+ T cells, regulatory T cells, natural killer cells and dendritic cells were identified. And two hub gene modules were found, in which six hub genes including APOL1, CCL17, RBP4, KRT15, KRT71, and KRT79 were significantly related to overall survival and were closely correlated with some certain TIICs in the validation of TIMER.ConclusionIn this study, four prognostic TIICs and six hub genes were found to be closely related to EEA. These findings provided new potential targets for EEA immunotherapy.
Highlights
Endometrial carcinoma is one of the most common tumors in the female reproductive system
The abundance ratio matrix of 22 Tumor-infiltrating immune cells (TIICs) was obtained from gene expression profiles of Abbreviations: EEA, Endometrioid endometrial adenocarcinoma; TIICs, tumorinfiltrating immune cells; TCGA, The Cancer Genome Atlas; FPKM, Fragments Per Kilobase of transcript per Million mapped reads; Tregs, regulatory T cells; LASSO, Least Absolute Shrinkage and Selector Operation regression analysis; DEGs, differentially expressed genes; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; Gene set enrichment analysis (GSEA), Gene Set Enrichment Analysis; PPI, Protein–protein interactions; MCODE, molecular complex detection plugin in Cytoscape software; UCEC, Uterine Corpus Endometrial Carcinoma
252 EEA samples were selected with p-value
Summary
Endometrial carcinoma is one of the most common tumors in the female reproductive system. Endometrioid endometrial adenocarcinoma (EEA) is the most common type of endometrial carcinoma, accounting for about 70–80% [3]. The survival rate of EEA patients can reach 85%, but it is less than 50% for the patients in advanced-stage with low benefits in present therapeutic strategies [4, 5]. The development of new treatment methods to further improve the survival rate of EEA patients is an urgent problem to be solved in the clinic. Endometrioid endometrial adenocarcinoma (EEA) is one of the most common tumors in the female reproductive system. With the further understanding of immune regulation mechanism in tumor microenvironment, immunotherapy is emerging in tumor treatment. There are few systematic studies on EEA immune infiltration
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