Abstract: Objective To investigate the metabolic features of obesity-driven endometrial cancer (EC). Methods A retrospective nested case-control study was conducted using clinical data retrieved from the hospital electronic medical record system for 315 patients diagnosed with EC between March 2020 and November 2024. Patients were stratified into an obesity-driven EC group (BMI≥28 kg/m², n=102) and a non-obesity EC group (BMI<28 kg/m², n=213) based on body mass index (BMI). Blood samples collected at the time of EC diagnosis were obtained from the hospital-standardized biobank and were assayed for metabolic indicators. Univariate and multivariate logistic regression analyses were performed to assess the impact of metabolic indicators on obesity-driven EC. Receiver operating characteristic (ROC) curves were generated to assess the discriminatory performance of these biomarkers. Results Among 315 EC patients, 102 (32.38%) were classified as obesity-driven EC. Compared to the non-obese EC group, the obesity-driven EC group showed significantly higher proportions of FIGO stage III-IV disease, type I histology, low-grade tumors , BMI, serum leptin, RETN, and triglycerides (TG) levels, together with lower adiponectin (ADPN) levels (all P<0.01). Multivariate logistic regression identified elevated BMI (OR=16.094), increased serum leptin (OR=1.370), decreased ADPN (OR=0.495), and elevated RETN (OR=1.285) as independent predictors of obesity-driven EC (all P<0.01). ROC analysis demonstrated that serum leptin, ADPN, and RETN exhibited areas under the curve (AUC) of 0.847, 0.822, and 0.812, respectively, indicating good discriminatory capacity. Conclusions The metabolic signature of obesity-driven EC is characterized by an imbalance in adipocyte-derived cytokines, specifically elevated serum leptin and RETN concomitant with reduced ADPN. Measurement of these biomarkers may aid in the identification of obesity-driven EC.

Key words: Obesity-driven endometrial cancer, Metabolic characteristics, Body mass index （BMI）, Adipocyte-derived cytokines