Clinical and laboratory significance of soluble claudin-5 and VEGF in ovarian cancer

Introduction. Claudin 5 is belongs to a family of transmembrane proteins mediating formation of tight junctions between cells, maintenance of cell polarity in epithelial and endothelial layers, regulation of cell membrane permeability, and control of signal transduction inside the cells. Results of a small number of studies show that vascular endothelial growth factor (VEGF) also affects formation of tight junctions, in particular through regulation of claudin 5 expression. In addition to their physiological functions, claudin 5 and VEGF play an important role in pathogenesis of various diseases including malignant neoplasms.
Aim. To study the levels of claudin 5 and VEGF in serum of patients with ovarian cancer and evaluate their clinical significance.
Materials and methods. In total, 123 patients with ovarian cancer (median age 54 years) and 32 control group healthy women (median age 54 years) were examined. Claudin 5 and VEGF levels in serum were measured prior to treatment using Human CLDN5 (Claudin 5) ELISA Kit (Elabscience, China) and Human VEGF Immunoassay (Quantikine®, R&D Systems, uSA) in accordance with the manufacturer’s instructions. Statistical analysis of the obtained data was performed using the GraphPad Prizm v. 10 software. The values were compared and their correlations quantified using nonparametric Mann–Whitney, Kruskal–Wallis tests and Spearman’s rank correlation coefficient. Overall survival was analyzed using the Kaplan–Meier method.
Results. Claudin 5 was found in serum of 97 % of patients with ovarian cancer and 94 % of the control group women. Median (1st quartile (Q1) – 3rd quartile (Q3)) level of claudin 5 in serum of healthy women was 0.77 (0.48–1.17) ng/mL, patients with ovarian cancer – 0.95 (0.43–1.77) mg/mL. ROC analysis of informational value of claudin 5 in ovarian cancer showed unsatisfactory diagnostic accuracy of the model (area under the ROC curve (AuC) 0.613 (95 % confidence interval (CI) 0.513–0.713); p = 0.049): for median threshold value of 0.95 ng/mL the assay had sensitivity of 50 % and specificity of 60 %. VEGF was found in all patients with ovarian cancer and healthy women; median (Q1–Q3) VEGF level in serum of healthy women was 45.6 (13.3–89.09) pg/mL and was statistically significantly lower than in patients with ovarian cancer: 274.7 ng/mL (199.0–472.5). ROC analysis for ovarian cancer showed good diagnostic accuracy of the model (AuC 0.942 (95 % CI 0.886–0.997); p <0.0001) which allows to use serum VEGF level as a diagnostic criterion. The best results for sensitivity and specificity (71 and 100 %, respectively) were obtained at VEGF threshold level of 226.2 pg/mL. Serum claudin 5 and VEGF levels are associated with ovarian cancer progression. However, claudin 5 and VEGF are not statistically significant prognostic markers for this disease.
Conclusion. Serum levels of VEGF and claudin 5 in patients with ovarian cancer are significantly higher than in control group women and positively correlate with each other. Additionally, VEGF has relatively good diagnostic characteristics compared to healthy women of the control group. VEGF and claudin 5 levels are associated with the presence of distant metastases which points at their potential role in tumor progression. However, at this research stage, these markers cannot be recommended as diagnostic or prognostic criteria in ovarian cancer and require further study.

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