Evaluating plasma adipokines and their cognate receptors, as biomarkers for non-invasive diagnosis of endometrial cancer.

Endometrial cancer (EC) is the most common gynaecological malignancy in developed countries. Early detection remains challenging, with no established plasma-based biomarkers for clinical use. This study aimed to evaluate plasma adipokines and their receptor expression as diagnostic biomarkers for EC. Plasma levels of leptin, soluble leptin receptor, visfatin, and asprosin were quantified in EC and control patients using ELISA. The Free Leptin Index (FLI) was calculated as a ratio of leptin to soluble leptin receptor. Gene expression of corresponding receptors, including leptin receptor (Ob-R), insulin receptor (INSR) glucagon-like peptide-1 receptor GLP-1 receptor (GLP-1R), and asprosin-associated receptors, Toll-like Receptor 4 (TLR4), protein tyrosine phosphatase receptor type D (PTPRD), and Olfactory receptor family 4 subfamily M member 1 (OR4M1) were assessed by RT-qPCR from total blood. Plasma leptin levels were significantly elevated in EC patients, with the FLI over four times higher than controls (P=0.008). Soluble leptin receptor levels trended lower in EC, though non- significantly. Visfatin and asprosin plasma levels showed non-significant elevations. Gene expression analyses revealed significantly increased levels of GLP-1R, TLR4 and PTPRD in EC patients; suggestive of a diagnostic potential. Notably, plasma biomarker levels were not independently correlated with body mass index (BMI). Elevated FLI and upregulation of adipokine receptor expression highlight the potential of combining plasma-based and molecular biomarkers for EC diagnosis. However, the lack of independence from BMI and conflicting literature underscore the need for larger, standardized studies to validate these findings and determine clinical applicability.