ANALYSIS OF PROGNOSIS AND IMMUNE MICROENVIRONMENT IN ENDOMETRIAL CARCINOMA WITH EMPHASIS ON CHROMATIN REGULATOR-RELATED GENES AND THE IMPACT OF PHYSICAL FITNESS IN FEMALE ATHLETES

Abstract

Objective: To develop a prognostic risk model for endometrial carcinoma (EC) focusing on chromatin regulator (CR) related genes and assess its correlation with the physical fitness levels in female athletes, utilizing data from The Cancer Genome Atlas (TCGA). Methods: We extracted clinical, tumor mutational burden (TMB), and transcriptome data for EC patients from the TCGA database. The data were analyzed through Cox univariate and Lasso-Cox multivariate analyses to construct a prognostic risk scoring model based on CR-related genes. The model's validity and independence as a prognostic tool were evaluated, alongside its clinical utility. Functional enrichment analyses and assessments of the immune microenvironment were conducted to understand the model's biological implications. Results: Patients were categorized into high- and low-risk groups based on median risk scores derived from the CR-related gene models. Survival analysis revealed significant differences in overall survival (OS) between the high- and low-risk groups among EC patients, including those identified as female athletes with varying levels of physical fitness. The CR-related risk score emerged as an independent predictor of OS. A nomogram was created to aid clinical decision-making. The gene models showed associations with TMB and variations in immune cell infiltration, notably reduced infiltration of activated CD4 memory and CD8 T cells in high-risk groups (P<0.05). TMB levels were significantly higher in low-risk groups, indicating potential links between risk scores, TMB, and the immune microenvironment in physically active female patients. Conclusion: This study successfully constructed three CR gene-related prognostic risk scoring models for EC, highlighting their potential as independent prognostic indicators. The findings suggest a significant interaction between CR gene-related risk scores, TMB, and the immune microenvironment, which may vary according to physical fitness levels in female athletes with EC, underscoring the importance of incorporating physical fitness considerations into prognostic assessments and personalized treatment strategies for EC patients.