Expression of exosomal microRNA in high-grade ovarian cancer and ovarian endometriotic cysts


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Abstract

Recently, exosomal microRNA has been considered a potential noninvasive biomarker of various proliferative processes, particularly affecting the female reproductive system. Objective: To investigate the potential of plasma exosomal microRNA expression in patients with serous ovarian cancer, extragenital endometriosis, and ovarian endometriotic cysts (OEC) as potential markers of these diseases. Materials and methods: The study included seven patients with histologically confirmed high-grade serous ovarian cancer, six women in a control group without this pathology ("Control-ovarian cancer"), six patients with OEC, and five women of reproductive age without this pathology ("Control-OEC"). The exosomes were isolated from the blood, and the composition of plasma-derived exosomal microRNAs was determined using next-generation sequencing. Results: Pairwise comparison of miRNA content in the groups "ovarian cancer" - "Control-ovarian cancer" and "OEC" - "Control-OEC" identified 22 and 13 differentially expressed miRNAs (DEM) with statistically significant 2-fold or more differences. Potential markers for ovarian cancer included miR-141-3p, -199a-5p, -200b-3p, -203a-3p, -224-5p, and -4488and for OEC, miR-92b-5p, -486-5p, -3184-3p, -4732-5p, and -4235p. Potential target genes were identified for DEM in each pair of groups. The intracellular signaling pathways most likely involved in the pathogenesis of ovarian cancer and OEC were searched based on their lists. Potential target genes of several signaling pathways regulated by one or more DEMs in ovarian cancer and OEC included AKT1, ATM, BARD1, BAX, BCL2, BRCA1, CASP3, CDK4, CHEK1, CHEK2, JAK1, MDM2, PLK1, PTEN, RB1, SMAD2, SMAD3, and TP53. Functional clustering of target genes showed their involvement in regulating signaling pathways of growth factors, cell cycle, apoptosis, and DNA repair. Conclusion: The detection of unique DEMs in plasma exosomes indicates the presence of specific changes in the microRNA profile characteristic of ovarian cancer and OEC. The listed exosomal microRNAs can be considered candidates for markers of the studied proliferative processes. Multiple interactions between the identified microRNA target genes indicate their significant contribution and joint involvement into proliferative processes in ovarian cancer and OEC.

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About the authors

Mania V. Iurova

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: m_yurova@oparina4.ru
PhD. Student at the Chair of Obstetrics, Gynecology, Perinatology and Reproductology

Chupalav M. Eldarov

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: ch_eldarov@oparina4.ru
PhD. (Bio), Senior Researcher at the Laboratory of Molecular Pathophysiolog

Mikhail Yu. Bobrov

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: mbobr@mail.ru
PhD. (Chemistry), Head of the Laboratory of Molecular Pathophysiology

Grigory N. Khabas

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: g_khabas@oparina4.ru
Ph.D., surgeon, oncologist, obstetrician-gynecologist, Head of the Department of Innovative Oncology and Gynecology

Stanislav V. Pavlovich

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: s_pavbvich@oparina4.ru
PhD, Academic Secretary

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