New opportunities for early prediction of precancerous and cancerous lesions of the cervix: risk stratification based on the analysis of gene methylation
AbstractNowadays, cervical cancer (CC) remains one of the urgent problems of world health. Today, close attention is paid to the organization of screening for CC and increasing the level of its predictive effectiveness. Thus, given the limited capabilities of already known screening methods, such as testing for HPV DNA and cytological examination, many researchers are studying the prospects for the development and introduction into clinical practice of new diagnostic methods that could complement or, possibly, a worthy alternative to conventional screening methods for cervical cancer. One of these methods may be the analysis of DNA methylation of certain genes, the modification of which is most characteristic of malignant neoplasms of the cervix. On the example of many studies, it was shown that the detection of abnormal methylation of various genes positively correlated not only with the risk of developing cervical cancer, but also with precancerous lesions of the cervix. This article presents the experience accumulated in the world of applying the analysis of hypermethylation of various panels of genes in relation to determining the risks of developing cervical cancer, HSIL and LSIL.
Keywords:squamous intraepithelial lesions; epigenetic changes; DNA methylation
Funding. The study had no sponsor support.
Conflict of interest. The authors declare no conflict of interest.
For citation: Andreev A.O., Bayramova G.R., Zaretsky A.R., Rebrikov D.V., Baranov I.I. New opportunities for early prediction of precancerous and cancerous lesions of the cervix: risk stratification based on the analysis of gene methylation. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2023; 11 (2): 44–9. DOI: https://doi.org/10.33029/2303-9698-2023-11-2-44-49 (in Russian)
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Если обратиться к статистическим показателям эффективности методов диагностики, то существуют убедительные данные, свидетельствующие о высоких уровнях чувствительности и специфичности анализа метилирования FAM19A4/miR124-2, соотносимые с жидкостной цитологией и тестированием на ДНК ВПЧ. Так, сообщается, что комбинированная чувствительность анализа метилирования FAM19A4/miR124-2 к раку шейки матки составила 95% (от 88 до 100%, по данным разных источников), для CIN III - 77% (от 71 до 82%), для CIN II - варьировала от 33,3 до 61,1% [6]. Общая специфичность FAM19A4/miR124-2 составляет 78,3%. Отрицательная прогностическая ценность достигла уровня 99,9% для рака шейки матки, 96,9% для ≥CIN III и 93,0% для ≥CIN II. При этом положительная прогностическая ценность составила 28,3% для ≥CIN III и 36,7% для ≥CIN II.
Заключение
По данным базы PubMed, за период с 2015 по 2023 г. опубликовано всего 22 работы по теме метилирования FAM19A4/mir124-2, ввиду чего становится очевидной научная перспектива дальнейших исследований по этой теме. При этом, несмотря на приведенные убедительные данные об эффективности использования тестов на метилирование ДНК, в будущем необходимо найти способ избегать компрометации результатов исследования вследствие возможного обнаружения физиологически метилированных форм ДНК.
Таким образом, анализ определения аномального метилирования FAM19A4/miR124-2 может служить не только новым эффективным дополнением к уже имеющимся скрининговым методам, а возможно, и будущей достойной альтернативой в проведении скрининга на РШМ.
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