vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2018-15-3-263-275vestim-447Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEОЦЕНКА ПРОГНОСТИЧЕСКОГО ЗНАЧЕНИЯ МЕТИЛИРОВАНИЯ ГЕНОВ CDKN2A И TIMP3 ПРИ РАКЕ МОЧЕВОГО ПУЗЫРЯASSESSMENT OF A PROGNOSTIC VALUE OF CDKN2A AND TIMP3 GENE METHYLATION IN BLADDER CANCERСмальМ. П.SmalM. P.

Смаль Маргарита Петровна – канд. биол. наук, ст. науч. сотрудник

ул. Академическая, 27, 220072, г. Минск

Marharyta P. Smal – Ph. D. (Biol.), Senior researcher

27, Akademicheskaya Str., 220072, Minsk

marharyta.smal@gmail.comНикитченкоН. В.NikitchenkoN. V.

Никитченко Наталья Васильевна – науч. сотрудник

ул. Академическая, 27, 220072, г. Минск

Nataliya V. Nikitchenko – Researcher

27, Akademicheskaya Str., 220072, Minsk

N.Nikitchenko@igc.byРолевичА. И.RolevichA. I.

Ролевич Александр Игоревич – канд. мед. наук, вед. науч. сотрудник

223040, агр. Лесной, Минский р-н

Alexander I. Rolevich – Ph. D. (Med.), Leading researcher

223040, Lesnoy, Minsk region

alexander.rolevich@gmail.comНабебинаТ. И.NabebinaT. I.

Набебина Татьяна Ивановна – канд. мед. наук, врач патогистологической лаборатории

223040, агр. Лесной, Минский р-н

Tatiana I. Nabebina – Ph. D. (Med.), pathohistologist

223040, Lesnoy, Minsk region

nabebina.t@yandex.byКрасныйС. А.KrasnyS. A.

Красный Сергей Анатольевич – член-корреспондент, д-р мед. наук, профессор, заместитель директора

223040, агр. Лесной, Минский р-н

Sergei A. Krasny – Corresponding Member, D. Sc. (Med.), Professor, Deputy Director

223040, Lesnoy, Minsk region

sergeykrasny@tut.byГончароваР. И.GoncharovaR. I.

Гончарова Роза Иосифовна – д-р биол. наук, профессор, заведующий лабораторией

ул. Академическая, 27, 220072, г. Минск

Roza I. Goncharova – D. Sc. (Biol.), Professor, Head of the Laboratory

27, Akademicheskaya Str., 220072, Minsk

R.Goncharova@igc.byИнститут генетики и цитологии НАН БеларусиInstitute of Genetics and Cytology of the National Academy of Sciences of BelarusРеспубликанский научно-практический центр онкологии и медицинской радиологии им. Н. Н. АлександроваN. N. Alexandrov National Cancer Centre201816092018153263275Copyright © Смаль М.П., Никитченко Н.В., Ролевич А.И., Набебина Т.И., Красный С.А., Гончарова Р.И., 20182018Смаль М.П., Никитченко Н.В., Ролевич А.И., Набебина Т.И., Красный С.А., Гончарова Р.И.Smal M.P., Nikitchenko N.V., Rolevich A.I., Nabebina T.I., Krasny S.A., Goncharova R.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/447

Одним из механизмов нарушения эпигенетической регуляции экспрессии генов является гиперметилирование промоторных областей генов-онкосупрессоров, которое часто наблюдается в злокачественных новообразованиях различной локализации. Профиль мутационных и эпигенетических изменений характеризует злокачественный потенциал опухоли, а также ее способность к инвазии и метастазированию.

Цель исследования состояла в определении прогностической роли статуса метилирования генов р16, p14ARF и TIMP3 при раке мочевого пузыря на примере выборки из 158 пациентов. Эпигенетические изменения исследованных генов наблюдались с частотой 11,4; 0 и 10,8 % соответственно и не зависели от клинико-морфологических характеристик.

Установлена статистически значимая ассоциация аномального метилирования генов р16 и TIMP3 с курением, что указывает на возможное влияние канцерогенов табачного дыма на возникновение данных эпигенетических изменений. Многофакторный регрессионный анализ пропорциональных рисков Кокса показал независимую прогностическую значимость гиперметилирования промоторной области гена р16 в отношении прогрессирования рака мочевого пузыря без мышечной инвазии (отношение рисков 6,84; 95 % ДИ 1,6–29,9; р = 0,011).

Применение полученных данных об эпигенетической изменчивости р16 позволит повысить точность прогноза клинического течения рака мочевого пузыря и подобрать адекватную тактику лечения.

Promoter hypermethylation of tumor suppressor genes is one of the mechanisms of epigenetic regulation disturbance of gene expression and is often observed in different cancer types. The profile of mutational and epigenetic changes characterizes a malignant potential of a tumor, as well as its ability to invade and metastasize.

The aim of the study was to determine a prognostic value of p16, p14ARF and TIMP3 gene methylation in the group of 158 bladder cancer patients. Epigenetic changes in these genes were observed with a frequency of 11.4, 0 and 10.8 %, respectively, and did not depend on clinic-morphological characteristics.

A statistically significant association of p16 and TIMP3 abnormal methylation with smoking was found, indicating a possible influence of tobacco smoke carcinogens on the occurrence of these epigenetic changes. In the multivariate Cox regression analysis, p16 promoter hypermethylation was an independent predictor for bladder cancer progression (HR 6.84; 95 % CI 1.6–29.9; р = 0.011).

The use of the data on the p16 methylation status may improve the accuracy of prognosis of the bladder cancer clinical course and the selection of appropriate treatment strategy.

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The authors declare that there are no conflicts of interest present.