Relationship between serum soluble HLA-G levels and clinico- pathological characteristics of endometrial cancer

This retrospective case-control study was performed to investigate the associations between serum soluble human leukocyte antigen-G (sHLA-G) concentrations and clinicopathological parameters in patients with endometrial cancer (EC). Between September 2022 and July 2025, EC patients who underwent hysteroscopy or surgical staging at the Department of Obstetrics and Gynecology, Kiang Wu Hospital were enrolled as the case group. Age-matched patients receiving hysteroscopy with pathologically confirmed benign endometrium during the same period served as the control group. Comprehensive clinical data and postoperative pathological reports of all EC patients were collected. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify serum sHLA-G concentrations in all participants. Immunohistochemistry was performed to detect HLA-G expression in tumour tissues. Histological subtypes were stratified according to the 2023 FIGO endometrial cancer risk classification into non-aggressive and aggressive histological subtypes. Exploratory receiver-operating characteristic (ROC) analysis was conducted for the aggressive subgroup; these ROC-derived metrics are hypothesis-generating only and lack independent external validation. No statistically significant difference in serum sHLA-G levels was observed between 55 EC patients and 56 control subjects ( p > 0.05). Patients with aggressive histological subtypes exhibited significantly higher serum sHLA-G levels than those with non-aggressive histological subtypes ( P = 0.033; n = 6 in the aggressive subgroup). Among 53 patients with endometrioid carcinoma, sHLA-G concentrations did not differ significantly across tumor differentiation grades (G1, G2, G3, p > 0.05). In the subgroup of 36 patients receiving complete surgical staging, serum sHLA-G showed no correlation with myometrial invasion depth (< 1/2 vs. > 1/2 myometrium, p > 0.05). Similarly, sHLA-G levels were comparable between patients with versus without lymphovascular space invasion (LVSI), and between patients with versus without lymph node metastasis (all p > 0.05). No significant association was observed between serum sHLA-G and tissue HLA-G immunohistochemical status. In conclusion, serum sHLA-G concentrations were not elevated in EC patients relative to individuals with benign endometrium. Within the endometrioid carcinoma subgroup, sHLA-G showed no significant correlation with tumor differentiation, LVSI or lymph node metastasis. An exploratory positive association was observed between higher serum sHLA-G and aggressive histological subtypes. This finding requires validation in larger independent cohorts and does not currently establish sHLA-G as a marker of tumour invasiveness or as a diagnostic or prognostic biomarker.