Preoperative serum PAK1, snail, and CXCL2 in endometrial cancer: diagnostic discrimination and association with tumor stage in a prospective case-control study

Epithelial-mesenchymal transition and chemokine signaling are implicated in endometrial carcinogenesis, yet the value of their circulating mediators as preoperative blood-based markers remains poorly defined. We evaluated preoperative serum p21-activated kinase 1 (PAK1), Snail, and C-X-C motif chemokine ligand 2 (CXCL2) in endometrial cancer to determine whether these three serum proteins discriminate endometrial cancer from benign gynecologic disease and whether they relate to established clinicopathological prognostic features. In this prospective, single-center case-control study, preoperative serum PAK1, Snail, and CXCL2 were quantified by enzyme-linked immunosorbent assay in 88 women with histologically confirmed endometrial cancer (predominantly endometrioid) and 87 women with benign gynecologic disease (benign controls). Group differences, receiver operating characteristic (ROC) analysis, multivariable logistic regression, and clinicopathological associations were assessed. To address the demographic imbalance between groups, additional sensitivity analyses were performed using age- and body mass index (BMI)-matched subgroups, a postmenopausal-restricted analysis, and covariate-adjusted (incremental) discrimination. Serum CXCL2 was substantially lower in cancer patients than in the benign controls (median 185.7 vs. 353.4 pg/mL; p < .001) and discriminated cancer with an area under the curve (AUC) of 0.923 (95% CI 0.877–0.970; sensitivity 86.4%, specificity 94.3%). This discrimination persisted in an age- and BMI-matched subgroup (AUC 0.958, 95% CI 0.906-1.000) and among postmenopausal women (AUC 0.926, 95% CI 0.878–0.974), and CXCL2 improved discrimination beyond age and BMI alone (AUC 0.841, 95% CI 0.781-0.900, to 0.953, 95% CI 0.920–0.985; DeLong p < .001). PAK1 and Snail did not differ univariably but contributed independently in a multivariable model that also retained CXCL2, BMI, and menopausal status (pseudo R² = 0.66). Within the cancer group, PAK1 was higher in FIGO stage II-III than stage I disease ( p = .011), whereas no marker varied by tumor grade. Preoperative serum CXCL2 was much lower in women with endometrial cancer and discriminated endometrial cancer cases from benign surgical controls (AUC 0.923, 95% CI 0.877–0.970); this separation held after we accounted for age, BMI, and menopausal status. Serum PAK1 was higher in advanced-stage tumors. These are exploratory, hypothesis-generating results that will need confirmation in an independent cohort and testing against molecular subtype and survival data.