Endometrial Cancer and the Glycoprotein Osteopontin: An Explorative Surgical Cohort Study on Potential Diagnostic Applications

Background/Objectives: One of the most prevalent gynecological diseases in developed nations is endometrial cancer (EC), whose incidence is steadily rising. Osteopontin (OPN) is a crucial extracellular matrix molecule linked to tumors. Our main goal was to investigate the potential relationship between OPN and EC, by comparing its levels in blood and endometrial tissue in 40 patients with malignant versus 40 with benign uterine disorders. Our secondary aim was to analyze OPN (in blood and endometrial tissue) and the levels of some related molecules (Cyclin-Dependent Kinase Inhibitor 3-CDKN3 and Integrin αvβ3, in endometrial tissue), also considering established serum tumor markers. Methods: Patients undergoing hysterectomy for EC (cases) or for benign diseases (controls) at the Department of Obstetrics and Gynecology of the AOU Maggiore della Carità, Novara (Italy), were recruited for this single-center prospective observational study. Results: The mean amount of OPN in blood and endometrium was significantly higher in cases than in controls (p < 0.0001). Integrin αvβ3 and CDKN3 were significantly higher in cases (p < 0.0001); no significant connections were found considering OPN, Integrin αvβ3, CDKN3 and weight, body mass index, age, thyroid-stimulating hormone (TSH), glycated hemoglobin, specific cancer staging/grading and molecular classification. Conclusions: These preliminary findings require validation in future prospective, independent cohorts. The levels of OPN, Integrin αvβ3, and CDKN3 were significantly elevated in cases compared to controls. No major confounding has been identified in preliminary evaluations, supporting their potential utility in a future diagnostic panel, though these findings require verification in larger cohorts.