V.I. Loginov1, I.V. Tereshkina2, D.N. Kushlinsky3, A.A. Alferov4, A.I. Koltunova5, N.A. Arzhanukhina6, D.V. Rogozhin7, E.A. Braga8, O.V. Kovaleva9, N.E. Kushlinskii10

1,4,8,10 Research Institute of General Pathology and Pathophysiology (Moscow, Russia)

2 A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of Russia
(Moscow, Russia)

3 Institute for advanced training of healthcare professionals of the Ministry of Health of the Khabarovsk Territory (Khabarovsk, Russia)

4–7,9,10 N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia (Moscow, Russia)

One of the most relevant areas of clinical and experimental oncology is the study of angiogenic factors and miRNAs, which play a key role in angiogenesis by regulating the proliferation, differentiation, apoptosis, and migration of endothelial cells, which is important in the development of malignant neoplasms. The aim of this work is to analyze the association of methylation levels of a group of microRNA genes in tumor tissue and metastases, taking into account the concentrations of VEGF in the blood plasma of patients with ovarian cancer. A statistically significant increase in methylation levels of 13 miRNA genes was found in primary tumor tissue compared to histologically unchanged ovarian tissue in patients with ovarian cancer (OC). At the same time, a statistically significant increase in the methylation levels of 8 miRNA genes (MIR124-1, MIR132, MIR148A, MIR34B/C, MIR9-3, MIR130B, MIR1258, MIR339) in the metastatic tissue was found compared to those in the primary tumor tissue of OC patients. In addition, a direct statistically significant correlation was found between the concentration of VEGF in the blood plasma of patients with OC and the levels of miRNA gene methylation in the tumor tissue: MIR124-2 (rs=0.55; p<0.05), MIR125B-1 (rs=0 .36; p<0.05) and MIR127 (rs=0.58; p<0.05).
A significant direct correlation was noted between the concentration of VEGF in the blood plasma of patients with OC and the levels of methylation of miRNA genes in the tissue of metastases: MIR124-2 (rs=0.48; p<0.05) and MIR148A (rs= 0.39; p<0.05). Also shown are significant differences in the median methylation of the miRNA genes MIR124-2, MIR127 and MIR193 in the primary tumor and the MIR148A gene in the tissue of metastases in groups of patients with OC, divided by the median of VEGF in blood plasma - less and more than 59.0 pg/ml. Clinical analysis of the association of the key angiogenesis activator VEGF in blood plasma with the levels of methylation of a group of microRNA genes in the tumor tissue and metastases in patients with OC suggests their role as promising prognostic markers.

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