[Association of fat distribution and TGR5 expression with clinicopathological features and prognosis in patients with...

Objective: To investigate the effects of visceral fat and subcutaneous fat distribution and the expression level of serum Takeda G protein-coupled receptor 5 (TGR5) on the clinicopathologic features and postoperative recurrence and metastasis of patients with endometrial cancer (EC). Methods: This was a retrospective cohort study. A total of 146 EC patients who underwent laparoscopic radical resection of EC at Northwest Women and Children's Hospital from March 2020 to March 2024 were enrolled as the EC group, and 153 concurrent patients with benign endometrial lesions were enrolled as the control group. The EC group was followed up for 1 year after the surgery to analyze the prognosis. Depending on whether recurrence and metastasis occurred, the EC group was further divided into the recurrence or metastasis subgroup (n=45) and the non-recurrence or metastasis subgroup (n=101). Age, obstetric history, body mass index (BMI), serum TGR5 level, visceral fat area (VFA) and subcutaneous fat area (SFA) were collected and compared between the recurrence or metastasis subgroup, non-recurrence or metastasis subgroup and the control group. The area under curve, sensitivity, specificity and the Youden index of the predictive value of TGR5 expression level, VFA level, SFA level, and BMI in patients in the EC group were analyzed using receiver operating characteristic (ROC) curves. Based on the cut-off value determined by the Youden index, the patients in the EC group were further classified into high-expression/high-level and low-expression/low-level groups. Univariate and multivariate Cox proportional hazards regression models were used to identify the risk factors for recurrence and metastasis of patients in the EC group in 1 year. The one-year recurrence and metastasis of EC patients with different serum TGR5 expression levels, VFA levels, SFA levels and BMI were analyzed, survival curves were plotted and data of recurrence-free survival (RFS) were obtained using the Kaplan-Meier method. ROC curves were constructed to evaluate the diagnostic efficacy of serum TGR5 expression level, VFA level, SFA level, BMI and their combined indicators. Results: The serum TGR5 expression level, VFA level, SFA level and BMI were significantly higher in the recurrence or metastasis subgroup compared to the non-recurrence or metastasis subgroup (all P<0.05). Furthermore, all four indicators in both the recurrence or metastasis subgroup and the non-recurrence or metastasis subgroup were significantly higher than those in the control group (all P<0.05). When the serum TGR5 expression level was 7.7 μg/L, the VFA level was 90.4 cm², the SFA level was 221.6 cm², and the BMI was 23.9 kg/m², the Youden index reached its maximum value for each respective parameter. Cox regression analyses revealed that serum TGR5≥7.7 μg/L (HR=6.382, 95%CI:2.151-18.939, P=0.001), VFA≥90.4 cm² (HR=6.914, 95%CI:2.279-20.979, P=0.001), SFA≥221.6 cm² (HR=7.520, 95%CI:2.414-23.421, P=0.001) and BMI≥23.9 kg/m² (HR=9.434, 95%CI:3.019-29.473, P<0.001) were risk factors for recurrence and metastasis within 1 year after surgery. The incidence of postoperative recurrence and metastasis in the high TGR5 expression group, high VFA level group and high SFA level group were significantly higher, while the RFS times were significantly shorter than those in the low TGR5 expression group, low VFA level group and low SFA level group (all P<0.05). ROC curve analysis showed that the above independent factors had good evaluation efficacy, and the combined detection was superior to single indicator detection. Conclusions: EC patients with high serum TGR5 expression level, VFA level and SFA level have a higher recurrence and metastasis rate. High serum TGR5 expression level, high VFA level, high SFA level and high BMI are risk factors for recurrence and metastasis within 1 year after radical resection of EC, and the diagnostic value of combined detection is superior to single indicator detection.