Bioinformatic Profiling Identifies Prognosis-Related Genes in the Immune Microenvironment of Endometrial Carcinoma

Abstract

Background: Endometrial carcinoma (EC) is a common malignancy of female genital system which exhibits a unique immune profile. It is a promising strategy to quantify immune patterns of EC for predicting prognosis and therapeutic efficiency. Here, we attempted to identify the possible immune microenvironment-related prognostic markers of EC. Methods: We obtained the RNA sequencing and corresponding clinical data of EC from TCGA database. Then, 3 immune scores based on the Estimation of STromal and immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm were computed. Correlation between above ESTIMATE scores and other immune-related scores, molecular subtypes, prognosis, and gene mutation status (including BRCA and TP53) were further analyzed. Afterwards, gene modules associated with the ESTIMATE scores were screened out through hierarchical clustering analysis and WGCNA. Differentially expressed analysis was performed and genes shared by the most relevant modules were found out. KEGG pathway enrichment analysis was conducted to explore the biological functions of those genes. Survival analysis was carried out to identify prognostic immune-related genes and GSE17025 database was used as external dataset for further validation.Results: The immune-related scores based on ESTIMATE algorithm was closely related to the immune microenvironment of EC. 3 gene modules that had the closest correlations with 3 ESTIMATE scores were obtained. 109 immune-related genes were preliminarily found out and 29 pathways were significantly enriched, most of which were associated with immune response. Univariate survival analysis revealed that there were 14 genes positively associated wicth both OS and PFS. Among which, 11 genes showed marked correlations with ImmuneScore values in GSE17025 database.Conclusion: Our current study profiled the immune status and identified 14 novel immune-related prognostic biomarkers for EC. Our findings may help to investigate the complicated tumor microenvironment and develop novel individualized therapeutic targets for EC.