oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2026-25-3-48-56oncotomsk-4319Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESМолекулярные особенности прогрессирования рака шейки матки I-II стадииMolecular features associated with progression of stage I-II cervical cancerhttps://orcid.org/0000-0002-1405-3723ПростакишинаЕ. А.ProstakishinaE. A.

Простакишина Елизавета Андреевна, младший научный сотрудник лаборатории биологии опухолевой прогрессии

Researcher ID (WOS): HCH-9870-2022. Author ID (Scopus): 57468497700. 

634009, г Томск, пер. Кооперативный, 5

Elizaveta A. Prostakishina, Junior Researcher, Laboratory of Cancer Progression Biology

Researcher ID (WOS): HCH-9870-2022. Author ID (Scopus): 57468497700.

5, Kooperativny st., Tomsk, 634009

elprostakishina@yandex.ruhttps://orcid.org/0000-0001-5926-2601ТрущукЮ. М.TrushchukYu. M.

Трущук Юлия Михайловна, онколог

Researcher ID (WOS): KQU-0974-2024. Author ID (Scopus): 57286591300. 

634009, г Томск, пер. Кооперативный, 5

Yulia M. Trushchuk, MD, Oncologist

Researcher ID (WOS): KQU-0974-2024. Author ID (Scopus): 57286591300. 

5, Kooperativny st., Tomsk, 634009

https://orcid.org/0000-0003-0194-6677КазаковаA. Д.KazakovaA. D.

Казакова Анна Дмитриевна, младший научный сотрудник лаборатории трансляционной клеточной и молекулярной биомедицины

Researcher ID (WOS): GYJ-4914-2022.Author ID (Scopus): 57735358300.

634050, г Томск, ул. Ленина, 36

Kazakova, Junior Researcher, Laboratory of Translational Cellular and Molecular Biomedicine

Researcher ID (WOS): GYJ-4914-2022. Author ID (Scopus): 57735358300. 

36, Lenina st., Tomsk, 634050

https://orcid.org/0000-0002-0646-6093ЯмщиковП. С.IamshikovP. S.

Ямщиков Павел Сергеевич, специалист по биоинформатике, лаборатория биологии опухолевой прогрессии

Researcher ID (WOS): AAE-3883-2022. Author ID (Scopus): 57468957700. 

634009, г Томск, пер. Кооперативный, 5

Pavel S. Iamshikov, Bioinformatic Specialist, Laboratory of Cancer Progression Biology).

Researcher ID (WOS): AAE-3883-2022.Author ID (Scopus): 57468957700. 

5, Kooperativny st., Tomsk, 634009

https://orcid.org/0009-0003-4139-2338КозловаП. К.KozlovaP. K.

Козлова Полина Константиновна, специалист по биоинформатике, лаборатория биологии опухолевой прогрессии

Researcher ID (WOS): JWA-4869-2024.

Polina K. Kozlova, Bioinformatic Specialist, Laboratory of Cancer Progression Biology

Researcher ID (WOS): JWA-4869-2024. \

5, Kooperativny st., Tomsk, 634009

ФатееваС. В.FateevaS. V.

Фатеева Светлана Викторовна, кандидат медицинских наук, врач ультразвуковой диагностики, Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук; ассистент кафедры лучевой диагностики и лучевой терапии, ФГБОУ ВО «Сибирский государственный медицинский университет» 

634009, г Томск, пер. Кооперативный, 5; 634050, г Томск, Московский тракт, 2

Svetlana V. Fateeva, MD, PhD, Physician, Cancer Research Institute, Тomsk National Research Medical Center, Russian Academy of Sciences; Assistant, Department of Radiology and Radiation Therapy, Siberian State Medical University 

5, Kooperativny st., Tomsk, 634009; 2, Moskovsky trakt, Tomsk, 634050

https://orcid.org/0000-0001-5758-7330ЛарионоваИ. В.LarionovaI. V.

Ларионова Ирина Валерьевна, кандидат медицинских наук, старший научный сотрудник лаборатории молекулярной терапии рака, Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук; старший научный сотрудник лаборатории трансляционной клеточной и молекулярной биомедицины, ФГАОУ ВО «Национальный исследовательский Томский государственный университет» 

Researcher ID (WOS): R-2391-2017. Author ID (Scopus): 57201182530.

634009, г Томск, пер. Кооперативный, 5; 634050, г Томск, ул. Ленина, 36

Irina V. Larionova, MD, PhD, Senior Researcher, Laboratory of Molecular Cancer Therapy, Cancer Research Institute, Тomsk National Research Medical Center, Russian Academy of Sciences; Senior Researcher, Laboratory of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University 

Researcher ID (WOS): R-2391-2017. Author ID (Scopus): 57201182530. 

5, Kooperativny st., Tomsk, 634009; 36, Lenina st., Tomsk, 634050

https://orcid.org/0000-0002-8194-2811ЧернышоваА. Л.ChernyshovaA. L.

Чернышова Алена Леонидовна, доктор медицинских наук, профессор РАН, профессор кафедры онкологии, ФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава России; директор Института онкологии и нейрохирургии, ФГБУ «Национальный медицинский исследовательский центр им. акад. Е.Н. Мешалкина»

Researcher ID (WOS): C-8608-2012. Author ID (Scopus): 55220758100.

630055, г Новосибирск, ул. Речкуновская, 15; 630091, г Новосибирск, Красный пр-т, 52

 

Alena L. Chernyshova, MD, DSc, Professor, Oncology Department, Novosibirsk State Medical University; Director, Institute of Oncology and Neurosurgery, E.N. Meshalkin National Medical Research Center

Researcher ID (WOS): C-8608-2012. Author ID (Scopus): 55220758100. 

15, Rechkunovskaya st., Novosibirsk, 630055; 52, Krasny prospekt, Novosibirsk, 630091

https://orcid.org/0000-0003-2923-9755ДенисовЕ. В.DenisovE. V.

Денисов Евгений Владимирович, доктор биологических наук, профессор РАН, заведующий лабораторией биологии опухолевой прогрессии

Researcher ID (WOS): C-8662-2012. Author ID (Scopus): 26653961800.

634009, г Томск, пер. Кооперативный, 5

Evgeny V. Denisov, DSc, Professor of the Russian Academy of Sciences, Head of the Laboratory of Cancer Progression Biology

Researcher ID (WOS): C-8662-2012. Author ID (Scopus): 26653961800.

5, Kooperativny st., Tomsk, 634009

Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesRussian FederationФГАОУ ВО «Национальный исследовательский Томский государственный университет»РоссияNational Research Tomsk State UniversityRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук; ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава РоссииРоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; Siberian State Medical UniversityRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук; ФГАОУ ВО «Национальный исследовательский Томский государственный университет»РоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; National Research Tomsk State UniversityRussian FederationФГБУ «Национальный медицинский исследовательский центр им. акад. Е.Н. Мешалкина» Минздрава России; ФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава РоссииРоссияE.N. Meshalkin national Medical Research Center, Ministry of Health of Russia; Novosibirsk State Medical University, Ministry of Health of RussiaRussian Federation2026110720262534856Copyright © Простакишина Е.А., Трущук Ю.М., Казакова A.Д., Ямщиков П.С., Козлова П.К., Фатеева С.В., Ларионова И.В., Чернышова А.Л., Денисов Е.В., 20262026Простакишина Е.А., Трущук Ю.М., Казакова A.Д., Ямщиков П.С., Козлова П.К., Фатеева С.В., Ларионова И.В., Чернышова А.Л., Денисов Е.В.Prostakishina E.A., Trushchuk Y.M., Kazakova A.D., Iamshikov P.S., Kozlova P.K., Fateeva S.V., Larionova I.V., Chernyshova A.L., Denisov E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/4319Введение

Введение. Эффективность лечения рака шейки матки (РШМ) I–II стадии остается недостаточно высокой из-за риска прогрессирования заболевания, что затрудняет выбор оптимальной тактики лечения и обусловливает необходимость поиска прогностических маркеров.

Цель исследования – выявление особенностей и маркеров прогрессирования РШМ I–II стадии.

Материал и методы

Материал и методы. Проведены анализ клинико-морфологических характеристик и полнотранскриптомное секвенирование; валидация результатов выполнена с использованием общедоступных данных из базы Атласа генома рака.

Результаты

Результаты. У больных с прогрессированием РШМ выявлена активация онкогенных (TNF-α через NFκВ, PI3K/AKT/mTOR и MTORC1, KRAS), метаболических (окислительное фосфорилирование, гликолиз и гипоксия) и иммунных (TGF-β, ответ на INFγ , INFα и IL2/STAT5) сигнальных путей, а также сигналинга фазы G2/М клеточного цикла посредством регуляции активности мишеней транскрипционных факторов E2F и MYC. Выявлено повышение экспрессии гена ITGA6 в опухолях пациенток с прогрессированием заболевания по сравнению со случаями с локализованным процессом.

Заключение

Заключение. Прогрессирование РШМ I–II стадии обусловлено комплексом пролиферативных, метаболических и иммуносупрессивных факторов, при этом ITGA6 является потенциальным прогностическим маркером данного заболевания.

Background

Background. The treatment efficacy of stage I-II cervical cancer (CC) remains suboptimal due to the risk of recurrence and metastasis, which complicates the selection of optimal treatment strategies and necessitates the search for prognostic markers.

This study aimed to identify molecular characteristics and markers associated with progressive stage I-II CC.

Material and Methods

Material and Methods. Clinical and morphological analyses and whole-transcriptome sequencing were performed, and publicly available data from the Cancer Genome Atlas (TCGA) database were used to validate the sequencing results.

Results

Results. Patients with progressive disease demonstrated activation of oncogenic (TNF-α via NF-κB, PI3K/AKT/mTOR, MTORC1, and KRAS), metabolic (oxidative phosphorylation, glycolysis, and hypoxia), immune (TGF-β, responses to IFNγ and IFNα, and IL2/STAT5), and G2/M cell cycle (through regulation of the E2F and MYC transcription factor targets) signaling pathways. the ITGA6 gene expression level was higher in tumors from patients with cervical cancer progression than in patients without cancer progression.

Conclusion

Conclusion. The progression of stage I-II cervical cancer is driven by a complex interplay of proliferative, metabolic, and immunosuppressive factors, with ITGA6 identified as a potential marker.

 

 

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