Re‐evaluating prognostic indicators: The critical role of body composition and gene expression in endometrial cancer outcomes

OBJECTIVE: To investigate the impact of body mass index (BMI), body composition (BC), and the expression of genes linked to obesity or lipid metabolism on the prognosis of endometrial cancer. METHODS: We conducted a comprehensive review of patients with confirmed endometrial cancer treated at the Pontificia Universidad Católica de Chile (PUC) and analyzed publicly available data from the endometrial cancer TCGA-UCEC cohort. BC was assessed using computed tomography (CT) scans, and gene expression analysis was performed using RNA-seq data. We evaluated the associations between BMI, BC, gene expression, and patient outcomes, including overall survival (OS) and progression-free survival (PFS). RESULTS: Our study included 127 patients (67 from PUC and 60 from TCGA-UCEC). BMI was not significantly associated with OS or PFS. However, BC metrics such as visceral adiposity and muscle mass were critical determinants of prognosis. We identified a 30-gene risk score significantly associated with poorer PFS and OS, independent of other factors. Analysis of the tumor microenvironment (TME) revealed significant differences in immune cell composition and functional states between high- and low-risk groups. CONCLUSION: BMI alone is not a significant prognostic factor in endometrial cancer. Comprehensive assessments of BC, gene expression profiles, and the TME provide more accurate prognostic information and highlight potential therapeutic targets. These findings advocate for a shift towards personalized medicine, incorporating detailed phenotyping and molecular profiling to improve patient outcomes.