N.E. Kushlinskii1, O.V. Kovaleva2, A.N. Grachev3, S.E. Kulikova4, F.A. Gugnin5, S.Yu. Nezhdanova6, D.N. Kushlinskiy7, I.V. Tereshkina8, N.N. Zybina9, E.S. Gershtein10, I.S. Stilidi11

1-3,10,11 N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia (Moscow, Russia)

1,4,6,8,10 Russian University of Medicine of the Ministry of Health of Russia (Moscow, Russia)

4,5 Moscow City Oncology Hospital No. 62 of the Moscow Health Department (Moscow, Russia)

7 Far Eastern State Medical University (Khabarovsk, Russia)

9 Nikiforov Russian Center for Emergency and Radiation Medicine EMERCOM of Russia (St. Petersburg, Russia)

1 kne3108@gmail.com, 2 ovkovaleva@gmail.com, 3 alexei.gratchev@gmail.com, 4 s_s76@mail.ru, 5 frol1999@inbox.ru, 6 nezhdsveta@ya.ru, 7 drkushlinskiy@gmail.com, 8 irinadari13@gmail.com, 9 zybinan@inbox.ru, 10 esgershtein@gmail.com, 11 ronc@list.ru

Cadherins are a large family of calcium-dependent molecules that play an important role in promoting cell-cell adhesion and maintaining the structural integrity of tissues. During the development of malignant tumors the expression of cadherins is often disrupted that leads to weakening of intercellular contacts and promotes tumor progression, including invasion and metastasis. Soluble forms of cadherins are formed by proteolytic cleavage of membrane-bound proteins or by alternative splicing. Cadherins play a significant role in the progression of ovarian cancer, one of the most aggressive and common types of gynecological cancer. However, there is a lack of studies on soluble forms of cadherins in blood serum.

The aim of this work is a comparative analysis of the content of soluble forms of E-, N-and VE-cadherins in healthy women, patients with cancer and benign ovarian tumors in order to evaluate their clinical value.

sE-cadherin, sN-cadherin, and sVE-cadherin concentrations were determined before treatment in blood serum of 56 ovarian cancer patients, 10 patients with benign ovarian tumors and 11 healthy control women. The frequency of sE-cadherin detection in the control practically healthy women comprised 100%; in patients with benign and malignant ovarian tumors it was 60% and 77% respectively. The frequency of sN-cadherin occurrence in the control group was lower (18%), in benign and malignant ovarian tumor groups it comprised 60% and 32% respectively. sVE-cadherin was detected in all samples studied. The cadherins content did not differ significantly between the studied groups, but some trends were observed. Thus, sE-cadherin content ws decreased in patients with ovarian tumors compared to the control group. An increase of sN-cadherin content was found in patients with benign ovarian tumors as compared to both the control, and ovarian cancer group. sVE-cadherin level was almost the same in all studied groups. No statistically significant associations of the studied cadherins content with age, disease stage, tumor size and differentiation degree, the presence of metastases or ascites was found. sVE-cadherin showed a slight  positive correlation with the presence of regional metastases (r=0.223. sE-cadherin and sN-cadherin serum concentrations that in the control group and in the group of patients with benign ovarian tumors did not correlate with each other. In the malignant ovarian tumors group a positive statistically significant correlation was observed between sE-cadherin and sN-cadherin content (r=0.478; p=0.0001).

Soluble forms of cadherins can play an important role in tumor progression and serve as diagnostic and prognostic markers for some neoplasms, but their role in ovarian cancer is currently unknown. Increasing the number of patients and further research aimed at understanding the molecular mechanisms of their release and developing new therapeutic approaches may help to improve the diagnostics and therapy of oncological diseases including ovarian cancer.

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