WIF1 gene methylation in endometrial pathology


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Abstract

Relevance. Wnt signaling pathway promotes proliferation, angiogenesis, and malignant transformation to endometrial cancer (EC). However, the role of epigenetic abnormalities of its inhibitory gene WIF1 in benign endometrial pathology remains unexplored. Aim. To investigate the WIF1 gene methylation status in different endometrial pathologies. Materials and methods. Methylation levels of the WIF1 gene were analyzed by bisulfite sequencing in samples of endometrial polyps (EP, n=60), endometrial hyperplasia (EH, n=35), chronic endometritis (CE, n=20), and normal proliferative stage endometrium (StP, n=20). Results. WIF1 gene methylation was detected in 80%, 72%, 61.7% of CE, EH, and EP samples and not found in normal StP endometrium (p&0.001). The highest methylation level was observed in EH samples. Patients with WIF1 gene methylation were 1.6 times more likely to have a history of intrauterine interventions. The number of intrauterine interventions correlated with methylation level. Conclusion. Epigenetic silencing of the WIF1 gene may play a significant role in forming EH and EP by activating the Wnt signaling pathway associated with an excessive proliferative and angiogenic activity. CE may be a risk factor for developing these diseases due to the induction of abnormal WIF1 gene methylation.

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About the authors

Lev A. Ashrafyan

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

Email: l_ashrafyan@oparina4.ru
Academician of the RAS, Dr. Med. Sci., Professor, Director of the Institute of Oncogynecology and Mammology

Vsevolod I. Kiselev

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

Email: vkis10@mail.ru
Dr. Bio. Sci., Corr. Member of the RAS, Deputy Director of the Institute of Gynecoloigy and Mammology

Galina E. Chernukha

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

Email: g_chernukha@oparina4.ru
Dr. Med. Sci., Professor

Ilya A. Ivanov

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

Email: doctor.i.ivanov@yandex.ru
Postgraduate Student at the Department of Gynecological Endocrinology

Andrey A. Poloznikov

National Medical Radiology Research Centre, Ministry of Health of Russia

Email: andrey.poloznikov@nmicr.ru
PhD. (chem. Sci.)., Deputy Director for Science

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