oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2026-25-1-85-94oncotomsk-4115Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESКоэкспрессия длинных некодирующих РНК MALAT1, HOTAIR, PVT1 с провоспалительными цитокинами в формировании платинорезистентного фенотипа при раке яичниковCoexpression of lncRNAs MALAT1, HOTAIR and PVT1 with pro-infammatory cytokines in the formation of a platinum-resistant phenotype of ovarian cancerhttps://orcid.org/0000-0001-5475-7031ДолговаД. Р.DolgovaD. R.

Долгова Динара Ришатовна, кандидат биологических наук, доцент, доцент кафедры физиологии и патофизиологии, Институт медицины, экологии и физической культуры Researcher ID (WOS): А-8492-2014. Author ID (Scopus): 55378365200

432017, г. Ульяновск, ул. Льва Толстого, 42

Dinara R. Dolgova, PhD, Associate Professor, Department of Physiology and Pathophysiology, Institute of Medicine, Ecology and Physical Education Researcher ID (WOS): A-8492-2014. Author ID (Scopus): 55378365200.

42, Lev Tolstoy St., Ulyanovsk, 432017

dolgova.dinara@yandex.ruhttps://orcid.org/0000-0001-6970-6659ГенингС. О.GeningS. O.

Генинг Снежанна Олеговна, кандидат медицинских наук, онколог Researcher ID (WOS): ABA-6267-2020. Author ID (Scopus): 55151451500 

121205, г. Москва, ул. Нобеля, 7

Snezhanna O. Gening, MD, PhD, Oncologist Researcher ID (WOS): ABA-6267-2020. Author ID (Scopus): 55151451500 

7, Nobel St., Moscow, 121205

https://orcid.org/0000-0002-1525-2070АнтонееваИ. И.AntoneevaI. I.

Антонеева Инна Ивановна, доктор медицинских наук, профессор, профессор кафедры физиологии и патофизиологии, Институт медицины, экологии и физической культуры; врач Researcher ID (WOS): А-8185-2014. Author ID (Scopus): 6504605612 

432017, г. Ульяновск, ул. Льва Толстого, 42;432017, г. Ульяновск, ул. 12 Сентября, 90

Inna I. Antoneeva, MD, DSc, Professor, Department of Physiology and Pathophysiology, Institute of Medicine, Ecology and Physical Education; Doctor Researcher ID (WOS): А-8185-2014. Author ID (Scopus): 6504605612 

42, Lev Tolstoy St., Ulyanovsk, 432017;90, 12 September St., Ulyanovsk, 432017

https://orcid.org/0000-0001-7559-5246АбакумоваТ. В.AbakumovaT. V.

Абакумова Татьяна Владимировна, доктор биологических наук, доцент, профессор кафедры физиологии и патофизиологии, Институт медицины, экологии и физической культуры Researcher ID (WOS): HJA-7814-2022. Author ID (Scopus): 37103623900 

432017, г. Ульяновск, ул. Льва Толстого, 42

Tatyana V. Abakumova, DSc, Professor, Department of Physiology and Pathophysiology, Institute of Medicine, Ecology and Physical Education Researcher ID (WOS): HJA-7814-2022. Author ID (Scopus): 37103623900. 

42, Lev Tolstoy St., Ulyanovsk, 432017

https://orcid.org/0000-0002-3908-0840МягдиеваИ. Р.MyagdievaI. R.

Мягдиева Ильсея Ринатовна, старший преподаватель кафедры физиологии и патофизиологии, Институт медицины, экологии и физической культуры Researcher ID (WOS): E-8062-2017. Author ID (Scopus): 58249336400 

432017, г. Ульяновск, ул. Льва Толстого, 42

Ilse R. Myagdieva, Senior Lecturer, Department of Physiology and Pathophysiology, Institute of Medicine, Ecology and Physical Education Researcher ID (WOS): E-8062-2017. Author ID (Scopus): 58249336400. 

42, Lev Tolstoy St., Ulyanovsk, 432017

https://orcid.org/0000-0002-5117-1382ГенингТ. П.GeningT. P.

Генинг Татьяна Петровна, доктор биологических наук, профессор, заведующая кафедрой физиологии и патофизиологии, Институт медицины, экологии и физической культуры Researcher ID (WOS): A-8486-2014. Author ID (Scopus): 6507217338. 

432017, г. Ульяновск, ул. Льва Толстого, 42

Tatyana P. Gening, DSc, Professor, Head of the Department of Physiology and Pathophysiology, Institute of Medicine, Ecology and Physical Education Researcher ID (WOS): A-8486-2014. Author ID (Scopus): 6507217338.

42, Lev Tolstoy St., Ulyanovsk, 432017

https://orcid.org/0009-0006-9032-0762СнехаНирмала ДарвинSnehaNirmala Darwin

Дарвин Нирмала Снеха, студентка 3-го курса медицинского факультета специальности «Лечебное дело» 

432017, г. Ульяновск, ул. Льва Толстого, 42

Darwin Nirmala Sneha, 3rd-year student, Faculty of Medicine, specializing in General Medicine 

42, Lev Tolstoy St., Ulyanovsk, 432017

ФГБОУ ВО «Ульяновский государственный университет»РоссияUlyanovsk State UniversityRussian FederationООО «Лучи Здоровье»РоссияLuchi Zdorovye LLCRussian FederationФГБОУ ВО «Ульяновский государственный университет»; ГУЗ «Областной клинический онкологический диспансер»РоссияUlyanovsk State University; Regional Clinical Oncology DispensaryRussian Federation2026070420262518594Copyright © Долгова Д.Р., Генинг С.О., Антонеева И.И., Абакумова Т.В., Мягдиева И.Р., Генинг Т.П., Снеха Н., 20262026Долгова Д.Р., Генинг С.О., Антонеева И.И., Абакумова Т.В., Мягдиева И.Р., Генинг Т.П., Снеха Н.Dolgova D.R., Gening S.O., Antoneeva I.I., Abakumova T.V., Myagdieva I.R., Gening T.P., Sneha N.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/4115

Введение. Экспрессия основных медиаторов воспалительного сигналинга – цитокинов и длинных некодирующих РНК (днРНК) – играет значительную роль в течении опухолевого процесса и формировании платинорезистентного фенотипа рака яичников (РЯ). Цель исследования – оценить коэкспрессию длинных некодирующих РНК HOTAIR, MALAT1, PVT1 с провоспалительными цитокинами в плазме крови как признак возможного формирования платинорезистентного фенотипа рака яичников. Материал и методы. В исследование включено 46 пациенток с первичным раком яичников, проходивших лечение в Ульяновском онкологическом диспансере в 2018–21 гг., и 12 пациенток с доброкачественными опухолями яичников (группа сравнения). Из 2 мл плазмы крови пациенток до начала лечения выделяли РНК с последующими обратной транскрипцией и полимеразной цепной реакцией для анализа экспрессии HOTAIR, MALAT1, PVT1. В плазме крови также определяли уровни цитокинов IL-1β, -10, -17A, -18. Пациентки c РЯ были разделены на 2 группы по продолжительности бесплатинового интервала. Результаты. Установлено, что экспрессия в плазме длинных некодирующих РНК HOTAIR, MALAT1, PVT1 у больных раком яичников значимо выше, чем в плазме у пациенток с доброкачественными опухолями яичников. Экспрессия HOTAIR в плазме крови также была выше при раке яичников III–IV стадии, чем при РЯ I–II стадии. У пациенток с платинорезистентным раком яичников был значимо ниже уровень IL-17A и IL-10 по сравнению с группой сравнения, но выше IL-1β и IL-10, чем у больных платиночувствительным РЯ. Установлена корреляция между экспрессией днРНК MALAT1 и уровнем цитокина IL-18 в сыворотке крови. Заключение. Уровень экспрессии днРНК PVT1 в сыворотке крови пациенток с РЯ коррелирует со временем выживания без прогрессирования и позволяет оценить вероятность рецидива заболевания. Сочетанный уровень коэкспрессии днРНК MALAT1 и IL-18 в сыворотке крови может быть использован как предиктивный маркер для выявления платинорезистентного РЯ, а их сочетанная гиперэкспрессия с провоспалительными цитокинами до начала химиотерапии обладает прогностическим потенциалом маркера платинорезистентности рака яичников. В модель оценки риска прогрессирования РЯ в первые 6 мес от постановки диагноза включены данные экспрессии MALAT1 и HOTAIR и сывороточные уровни IL-1β, -18 до начала терапии, при этом значение коэффициента (К) выше 1,65 свидетельствует о высоком риске прогрессирования заболевания.

Background. Expression of the main mediators of infammatory signaling – cytokines and long non-coding RNAs (lncRNAs) – determines the course of the tumor process and the formation of a platinum-insensitive phenotype in ovarian cancer. The aim of the study was to evaluate the co-expression of long non-coding RNAs HOTAIR, MALAT1, PVT1 with proinfammatory cytokines in blood plasma during the formation of a platinum-insensitive phenotype in ovarian cancer. Material and Methods. The study included 46 patients with primary ovarian cancer treated at the Ulyanovsk Oncology Center in 2018–2020. RNA was isolated from 2 ml of patients’ blood plasma before treatment, followed by reverse transcription and polymerase chain reaction to analyze the expression of HOTAIR, MALAT1, and PVT1. Plasma levels of the cytokines IL-1β, -10, -17A, and -18 were also determined. Ovarian cancer patients were divided into 2 groups based on the duration of the platinum-free interval. Results. Plasma expression of long non-coding RNAs (lncRNAs) HOTAIR, MALAT1, and PVT1 was found to be signifcantly higher in patients with ovarian cancer than in patients with benign ovarian tumors. Plasma HOTAIR expression was also higher in stages III–IV ovarian cancer compared to stages I–II. Patients with platinum-insensitive ovarian cancer had signifcantly lower levels of IL-17A and IL-10 compared to patients in the comparison group, but higher levels of IL-1β and IL-10 compared to patients in the platinum-sensitive group. A correlation was found between the levels of lncRNA MALAT1 and IL-18. Conclusion. The serum expression level of PVT1 lncRNA in ovarian cancer patients correlates with progression-free survival and allows for assessing the likelihood of disease recurrence. Serum coexpression of MALAT1 and IL-18 lncRNAs can be used as a predictive marker for identifying platinuminsensitive ovarian cancer. Their combined overexpression with proinfammatory cytokines and IL-1β before chemotherapy has prognostic potential as a marker of platinum resistance in ovarian cancer. A prognostic model for assessing the risk of cancer progression in the frst 6 months after diagnosis includes MALAT1 and HOTAIR expression data at the start of therapy and serum IL-1β and -18 levels. A K-value above 1.65 indicates a high risk of disease progression.

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