Increased serum galectin-3 levels is an unfavorable prognostic factor in epithelial ovarian cancer

Background: Ovarian cancer is one of the most aggressive gynecological malignancies with a high mortality rate related to delayed diagnosis and high rates of resistance to conventional therapies. Results of clinical trials indicate that soluble galectin-3 could be considered as a potentially significant biomarker for malignant neoplasms of various locations. Its increased serum levels are frequently associated with aggressive tumors, risk of metastasis, resistance to therapy, and poor prognosis. However, data on its role and diagnostic value in ovarian cancer remains limited and contradictory. Aim: To analyze the diagnostic and prognostic value of the soluble galectin-3 in patients with various ovarian neoplasms. Methods: This retrospective study included 176 patients with ovarian tumors and 20 healthy donors who were examined and treated from January 2017 to December 2024 at the N. N. Blokhin National Medical Research Center of Oncology and Khabarovsk Territory Regional Clinical Center of Oncology. In all patients, the diagnosis was confirmed by morphological examination of the tumor according to the 2020 World Health Organization (WHO) Classification of Female Genital Tumors. Serum levels of soluble galectin-3 were measured in samples obtained before the initiation of specific treatment with the Human Galectin-3 Quantikine ELISA enzyme immunoassay kit (RD Systems, USA) in accordance with the manufacturer's instructions. Measurements were performed on a BEP 2000 Advance automated enzyme immunoassay analyzer (Siemens Healthcare Diagnostics, Germany) according to the manufacturer’s specifications. Results: One hundred and sixteen patients (116/176) had epithelial ovarian cancer (EOC), 6/176 had non-epithelial ovarian cancer (NEOC), 32/176 were diagnosed with benign ovarian tumors (BOT), and 22/176 with borderline ovarian tumors (BLOT). In the healthy controls, the median galectin-3 level was 8.02 ng/mL being significantly lower than that in the patients with EOC (10.35 ng/mL) (p = 0.0219). In the BOT group, the median galectin-3 level was 7.43 ng/mL, in the BLOT group 7.22 ng/mL, and in the NEOC group 5.49 ng/mL (p 0,999 for all comparisons to the control group). The ROC analysis demonstrated a moderate diagnostic significance of galectin-3 for EOC, with the area under the curve (AUC) of 0.702 and 95% confidence interval (CI) of 0.585 to 0.818 (p = 0.004). With a threshold value of galectin-3 concentration of 8.84 ng/mL, the test sensitivity was 62.93% and specificity 65%. If the median value were used as a cutoff, the sensitivity decreased to 50%, while the specificity increased to 75%. In the EOC group the galectin-3 levels were significantly associated with the patients age, in those above 57 of age its median value was 11.69 ng/mL, being significantly higher compared to the patients ≤ 57 years of age (9.03 ng/mL, p = 0.009). No associations were found between galectin-3 levels and other clinical and morphological characteristics, such as tumor size, disease stage, cancer spreading / metastasis). Depending on the histological type of epithelial tumors, median galectin-3 levels ranged from 9.64 ng/mL (serous type) to 13.18 ng/ml (clear cell type), but the differences were not significant (p = 0.358). In the univariate and multivariate analysis, elevated galectin-3 levels were significant predictors of unfavorable outcome (hazard ratio [HR]: 2.246, p = 0.046 and HR: 1.137, p = 0.017, respectively). Conclusion: Elevated soluble galectin-3 levels is a predictor of unfavorable prognosis in EOC. High serum concentration of this protein may be a promising additional diagnostic marker for EOC.