Expression of glucocorticoid receptor is associated with aggressive primary endometrial cancer with higher EMT phenotype and stemness

Background: Endometrial cancer (EC) is a gynecologic malignancy, with an increasing incidence and disease-associated mortality, worldwide. While the role of steroid hormone receptors in EC has been widely studied, the contribution of glucocorticoid receptor (GCR) to EC progression remains unclear. Methods: This study analyzed the gene expression of 507 primary EC samples from the Cancer Genome Atlas (TCGA) database. Samples were categorized into glucocorticoid receptor high (GCRH ) and Low (GCRL) groups based on mean transcript expression levels. The study evaluated correlations with clinical parameters, immune profiling, epithelial-mesenchymal transition (EMT), cancer stemness, angiogenesis and survival. Additionally, druggable targets associated with GCR were identified. Results: High GCR expression was linked to an aggressive EC phenotype, characterized by enhanced EMT, increased cancer stemness and increased angiogenesis. Tumors in the GCRH group exhibited a more immunosuppressive microenvironment, with enrichment of M2 macrophages, contributing to tumor progression and poorer clinical outcomes. Furthermore, 31 cancer driver genes and 25 druggable targets were identified. Conclusions: Our findings suggest that high GCR expression in EC is associated with poor prognosis due to its role in EMT, stemness and immune modulation. This highlights GCR as a potential biomarker for aggressive EC and a target for therapeutic intervention.