Bioinformatic profiling identifies prognosis-related genes in the immune microenvironment of endometrial carcinoma

Abstract

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. 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 weighted gene co-expression network analysis (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 further used to confirm the correlation between immune-related genes and the ImmuneScore. 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 with both OS and PFS. Among which, 11 genes showed marked correlations with ImmuneScore values in GSE17025 database. 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.

Development and validation of matrix metalloproteinase for predicting prognosis and tumour microenvironment immune profiles in uterine corpus endometrial carcinoma

“…Accumulating evidence indicates that the expression profile plays an indispensable role in inflammation, immunity, and inhibition of tumour progression 7 , especially in the development and progression of digestive tract tumours 9 , 40 , 41 ; however, there are no related studies on EC. Furthermore, most studies have focused on a single TME cell type or single protease, but the overall TME infiltration characteristics mediated by the combined effects of multiple MMPs have not been comprehensively recognized 4 . In this study, we analysed the clinical information and transcriptome data of EC patients from TCGA, and identified three distinct MMP expression patterns which displayed differences in immune cell infiltration and different disease prognosis.…”

“…Thus, there is a necessity for accurate screening tools to identify early EC patients. Recently, numerous studies have demonstrated a correlation between matrix metalloproteinases (MMPs) and EC 3 , 4 . Therefore, the functional roles and regulatory mechanisms of MMPs in EC need to be further investigated, and it is crucial to elucidate the association between MMPs and prognosis of EC.…”

Natural Kinase Inhibitors for the Treatment and Management of Endometrial/Uterine Cancer: Preclinical to Clinical Studies

“…Cells like endothelial cells, macrophages, myofibroblasts, and inflammatory cells communicate via cytokines, ligands receptors, and growth factors with EC cells and create a suitable microenvironment for tumor cell invasion and metastasis. The factors of microenvironment-derived signals and stromal cell-derived proteins are potential targets as biomarkers for the detection of metastatic EC ( Cheng et al, 2021 ).…”

Mechanism of action of icaritin on uterine corpus endometrial carcinoma based on network pharmacology and experimental evaluation

“…The morbidity and mortality of UCEC has shown an increasing trend worldwide in recent years ( 2 ). Surgery combined with adjuvant therapy (radiotherapy and/or chemotherapy) is the standard treatment for UCEC ( 3 ).…”