The Impact of Osteopontin and Galectin-7 on the Preoperative Diagnosis of Ovarian Tumors: A Case–Control Study

<b>Background/Objectives</b>: Accurate preoperative discrimination between women with ovarian pathology and healthy controls, as well as between benign and malignant ovarian tumors, remains challenging. This study aimed to evaluate the usefulness of osteopontin and galectin-7 on the diagnosis of ovarian tumors. <b>Methods</b>: This prospective single-center case-control study was conducted at the Third Department of Obstetrics & Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, between 2018 and 2024. Preoperative serum levels of osteopontin, galectin-7, and established tumor markers (CA-125, CA19-9, CA15-3, CEA, AFP) were analyzed. Biomarker distributions were compared using non-parametric tests. Associations with clinical variables were explored using correlation analyses. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess diagnostic performance. <b>Results</b>: The study population included 116 women: 52 healthy controls, 45 patients with benign ovarian tumors, and 19 patients with malignant ovarian tumors. Serum osteopontin and galectin-7 levels did not differ significantly between control and study group (<i>p</i> = 0.562 and <i>p</i> = 0.138, respectively), nor between benign and malignant tumors (<i>p</i> = 0.784 and <i>p</i> = 0.140, respectively). Osteopontin showed no discriminatory ability (AUC = 0.47), while galectin-7 demonstrated weak discrimination (AUC = 0.63). A combined model yielded modest improvement (AUC = 0.69), remaining below clinically meaningful thresholds. CA-125 was the only biomarker significantly associated with malignancy (OR = 1.03, <i>p</i> = 0.038). Galectin-7 levels were higher in premenopausal women and inversely correlated with age, suggesting demographic rather than malignant influence. <b>Conclusions</b>: Despite strong biological relevance, circulating osteopontin and galectin-7 did not provide meaningful diagnostic discrimination between women with ovarian pathology and healthy controls or between benign and malignant ovarian tumors. CA-125 remained the most informative serum marker in this setting. Future efforts should focus on multi-marker strategies integrated with imaging and clinical assessment.