cancerspЮжно-Российский онкологический журнал/ South Russian Journal of CancerSouth Russian Journal of Cancer2686-9039АНО "Перспективы онкологии"10.37748/2686-9039-2026-7-3-4QEXQOEcancersp-479Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПоловой диморфизм митохондриального стероидного профиля при метастатическом раке прямой кишкиSexual dimorphism of the mitochondrial steroid profile in metastatic rectal cancerhttps://orcid.org/0000-0003-3061-6108КитО. И.KitO. I.

Кит Олег Иванович – д.м.н., академик РАН, профессор, генеральный директор

г. Ростов-на-Дону

AuthorID: 343182

Scopus Author ID: 55994103100

WoS ResearcherID: U-2241-2017

Oleg I. Kit – Dr. Sci. (Medicine), Academician of the Russian Academy of Sciences, Professor, Director General

Rostov-on-Don

AuthorID: 343182

Scopus Author ID: 55994103100

WoS ResearcherID: U-2241-2017

https://orcid.org/0000-0003-3618-6890ФранциянцЕ. М.FrantsiyantsE. M.

Франциянц Елена Михайловна – д.б.н., профессор, заместитель генерального директора по науке

г. Ростов-на-Дону

AuthorID: 462868

Scopus Author ID: 55890047700

WoS ResearcherID: Y-1491-2018

Elena M. Frantsiyants – Dr. Sci. (Biology), Professor, Deputy General Director for Science

Rostov-on-Don

Author ID: 462868

Scopus Author ID: 55890047700

WoS ResearcherID: Y-1491-2018

https://orcid.org/0000-0002-2302-8271БандовкинаВ. А.BandovkinaV. A.

Бандовкина Валерия Ахтямовна – д.б.н., доцент, ведущий научный сотрудник лаборатории изучения патогенеза злокачественных опухолей

344037, г. Ростов-на-Дону, ул. 14 линия, д. 63

г. Ростов-на-Дону

AuthorID: 696989

Scopus Author ID: 57194276288

WoS ResearcherID: AAG-8708-2019

Valerija A. Bandovkina – Dr. Sci. (Biology), Leading Researcher at the Laboratory of Malignant Tumor Pathogenesis Study

Rostov-on-Don

AuthorID: 696989

Scopus Author ID: 57194276288

valerryana@yandex.ru.ruhttps://orcid.org/0000-0002-0796-3307ИльченкоС. А.IlchenkoS. A.

Ильченко Сергей Александрович – к.м.н., врач-онколог отделения абдоминальной онкологии №1, заместитель генерального директора по образовательной деятельности

г. Ростов-на-Дону

AuthorID: 705986

Scopus Author ID: 57201300417

Sergey A. Ilchenko – Cand. Sci. (Medicine), oncologist at the Abdominal Oncology Department №1, Deputy Director General for Educational Activities

Rostov-on-Don

AuthorID: 705986

Scopus Author ID: 57201300417

https://orcid.org/0000-0002-7395-3086НескубинаИ. В.NeskubinaI. V.

Нескубина Ирина Валерьевна – д.б.н., старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей

г. Ростов-на-Дону

AuthorID: 794688

Scopus Author ID: 6507509066

WoS ResearcherID: AAG-8731-2019

Irina V. Neskubina – Dr. Sci. (Biology), Senior Researcher at the Laboratory of Malignant Tumor Pathogenesis Study

Rostov-on-Don

AuthorID: 794688

Scopus Author ID: 6507509066

WoS ResearcherID: AAG-8731-2019

https://orcid.org/0000-0003-2943-7655ШихляроваА. И.ShikhlyarovaA. I.

Шихлярова Алла Ивановна – д.б.н., профессор, старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей

г. Ростов-на-Дону

AuthorID: 482103

Scopus AuthorID: 6507723229

WoS ResearcherID: Y-6275-2018

Alla I. Shikhlyarova – Dr. Sci. (Biology), Professor, Senior Researcher, Laboratory of Malignant Tumor Pathogenesis Study

Rostov-on-Don

AuthorID: 482103

Scopus AuthorID: 6507723229

WoS ResearcherID: Y-6275-2018

https://orcid.org/0000-0001-6265-8500ГорошинскаяИ. А.GoroshinskayaI. A.

Горошинская Ирина Александровна – д.б.н., профессор, старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей

г. Ростов-на-Дону

Author ID: 79968

Scopus Author ID: 6602191458

WoS ResearcherID: Y-2277-2018

Irina A Goroshinskaya – Dr. Sci. (Biology), Professor, Senior Researcher at the Laboratory of Malignant Tumor Pathogenesis Study

Rostov-on-Don

Author ID: 79968

Scopus Author ID: 6602191458

WoS ResearcherID: Y-2277-2018

https://orcid.org/0000-0002-0068-0881УшаковаН. Д.UshakovaN. D.

Ушакова Наталья Дмитриевна – д.м.н., профессор, врач анестезиолог-реаниматолог отделения анестезиологии и реанимации с палатами интенсивной терапии

г. Ростов-на-Дону

AuthorID: 571594

Scopus Author ID: 8210961900

WoS ResearcherID: L-6049-2017

Nataliya D. Ushakova – Dr. Sci. (Medicine), Professor, Anesthesiologist-Resuscitator of the Department of Anesthesiology and Resuscitation

Rostov-on-Don

AuthorID: 571594

Scopus Author ID: 8210961900

WoS ResearcherID: L-6049-2017

ФоменкоЮ. А.FomenkoYu. A.

Фоменко Юрий Александрович – к.м.н., заместитель генерального директора по клинико-экспертной работе

г. Ростов-на-Дону

AuthorID: 462430

Yurii A. Fomenko – Cand. Sci. (Medicine), Deputy Director for Clinical Expertise Work

Rostov-on-Don

AuthorID: 462430

https://orcid.org/0009-0005-6923-802XЛегенькоН. Н.LegenkoN. N.

Легенько Николай Николаевич – аспирант

г. Ростов-на-Дону

AuthorID: 1337056

Nikolay N. Legenko – PhD student

Rostov-on-Don

AuthorID: 1337056

Национальный медицинский исследовательский центр онкологии Министерства здравоохранения Российской ФедерацииРоссияNational Medical Research Centre for OncologyRussian Federation202606092026734559Copyright © Кит О.И., Франциянц Е.М., Бандовкина В.А., Ильченко С.А., Нескубина И.В., Шихлярова А.И., Горошинская И.А., Ушакова Н.Д., Фоменко Ю.А., Легенько Н.Н., 20262026Кит О.И., Франциянц Е.М., Бандовкина В.А., Ильченко С.А., Нескубина И.В., Шихлярова А.И., Горошинская И.А., Ушакова Н.Д., Фоменко Ю.А., Легенько Н.Н.Kit O.I., Frantsiyants E.M., Bandovkina V.A., Ilchenko S.A., Neskubina I.V., Shikhlyarova A.I., Goroshinskaya I.A., Ushakova N.D., Fomenko Y.A., Legenko N.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.cancersp.com/jour/article/view/479Цель исследования

Цель исследования. Определить половые особенности содержания стероидных гормонов и их рецепторов в митохондриях, выделенных из опухолевой ткани и линии резекции, у больных раком прямой кишки (РПК) в зависимости от наличия или отсутствия метастазов.

Пациенты и методы

Пациенты и методы. В исследование включены 48 пациентов больных РПК: 24 мужчины и 24 женщины. Пациенты были разделены на 4 группы, в каждой группе по 12 пациентов имели локализованную форму (T2–3N0M0) и по 12 – метастатическую (T2–3N1M0). Группы (мужчины/женщины, с метастазами/без) были сопоставимы по возрасту. Средний возраст пациентов составил 66 (58–73) лет. Из клеток опухоли и линии резекции прямой кишки методом дифференциального центрифугирования выделяли митохондрии. С помощью ИФА (наборы (Cusabio, Китай)) определяли уровни эстрадиола, эстрона, свободного эстриола, тестостерона, прогестерона, кортизола, холестерина и рецепторов ERα, ERβ, RA, RP4. Статистика: программа Statistica 10.

Результаты

Результаты. Установлены противоположные в зависимости от пола пациентов изменения гормонального про- филя при метастазировании. У мужчин с метастазами в митохондриях опухоли выше уровни тестостерона, холестерина и рецепторов (RA, RP4, ERα) в 1,7–4,5 раза, но уровень свободного эстриола ниже в 1,6 раза. У женщин метастазы ассоциированы со снижением в митохондриях тестостерона и рецепторов ERα и ERβ в 2,5–9,6 раза на фоне повышения уровня свободного эстриола в 2,3 раза и холестерина в 8 раз. В митохондриях линии резекции метастатический процесс частично нивелирует исходные половые различия.

Заключение

Заключение. При метастазирующем РПК у мужчин и женщин активируются противоположные программы митохондриальной адаптации. У женщин метастазирование ассоциировано со снижением андрогенной и эстрогенной сигнализации, на фоне высокого эстриола, у мужчин – с усилением андрогенного пути и синтетических процессов. Наблюдается частичное нивелирование половых различий в стероидном профиле линии резекции, что отражает системную метаболическую перестройку, поддерживающую агрессивный фенотип опухоли. Результаты исследования свидетельствуют о возможности использования митохондриальных биомаркеров для прогнозирования развития РПК, однако необходима дальнейшая валидация в клинических исследованиях.

Purpose of the study

Purpose of the study. To determine the sex-specific features of the content of steroid hormones and their receptors in mitochondria isolated from tumor tissue and the resection line in patients with rectal cancer (RC), depending on the presence or absence of metastases.

Patients and methods

Patients and methods. The study included 48 patients with RC: 24 men and 24 women. In each group, 12 patients had a localized form (stage T2–3N0M0) and 12 had a metastatic form (stage T2–3N1M0). The groups (men/women, with/without metastases) were comparable in age. The median patient age was 66 (range 58–73) years. Mitochondria were isolated from tumor cells and the resection line of the rectum by differential centrifugation. The levels of estradiol (E2), estrone (E1), free estriol (fE3), testosterone (T), progesterone (P4), cortisol, cholesterol, and receptors (ERα, ERβ, RA, RP4) were determined using ELISA kits (Cusabio, China). Statistical analysis was performed using Statistica 10 software.

Results

Results. Opposite sex-dependent changes in the hormonal profile during metastasis were established. In men with metastases, mitochondrial levels of testosterone, cholesterol, and receptors (RA, RP4, ERα) were 1.7–4.5‑fold higher, while free estriol was 1.6‑fold lower. In women, metastases were associated with a 2.5–9.6‑fold decrease in mitochondrial testosterone, ERα, and ERβ levels against a background of a 2.3‑fold increase in free estriol and an 8‑fold increase in cholesterol. In mitochondria from the resection line, the metastatic process partially neutralized the initial sex differences.

Conclusion

Conclusion. In metastatic RC, opposite programs of mitochondrial adaptation are activated in men and women. In women, metastasis is associated with a decrease in androgen and estrogen signaling against a background of high estriol, while in men, it is linked to the enhancement of the androgen pathway and synthetic processes. A partial leveling of sex differences in the steroid profile of the resection line is observed, reflecting a systemic metabolic reprogramming that supports an aggressive tumor phenotype. The study findings suggest that mitochondrial biomarkers may have potential for predicting the development of RC; however, further validation in clinical studies is required.

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