Identification and Clinical Validation of Key Immune Cells in Endometrial Cancer: A Focus on Mast Cells and Dendritic Cells

Objective Identify key immune cells in endometrial cancer (EC) using bioinformatics and validate findings. Methods The CIBERSORT algorithm analyzed 22 immune cell subtypes based on GEO and TCGA datasets. Transcriptomics was performed on 13 EC tumors and 6 adjacent non-tumorous tissues (ANT). Immunohistochemistry (IHC) was conducted on 50 EC and 15 ANT samples, correlating with clinical features. Results Mast cells (MCs) and dendritic cells (DCs) were dysregulated. Transcriptomics identified nine signature genes differentially expressed for MCs and DCs. MC-specific genes (e.g., CMA1, CTSG, CPA3) were downregulated in EC, enriched in secretory granule function and pathways like renin-angiotensin system. DC-associated genes (e.g., CAPG, CCNA1, TNFAIP2) were upregulated, enriched in chemotaxis and cytokine interactions. IHC confirmed significantly reduced MC marker CD117 in EC, correlating with higher BMI, advanced FIGO stage, and metastasis (P < 0.05). Conversely, DC marker CD11c was elevated, associated with advanced stage and metastasis (P < 0.05). Conclusion Our findings identify MCs and DCs as pivotal immune cells in endometrial carcinoma, with MC suppression and DC-driven pro-tumorigenic activity showing significant correlations with advanced clinicopathological features. These immune subsets and their associated signature genes may serve as prognostic biomarkers and therapeutic targets for remodeling the EC microenvironment.