oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2018-17-4-41-47oncotomsk-814Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESСВЯЗЬ МЕЖДУ РЕГУЛИРУЮЩИМИ БЕЛКАМИ АУТОФАГИИ M-TOR И BECLIN-1 И ПАРАМЕТРАМИ ЛИМФОГЕННОГО МЕТАСТАЗИРОВАНИЯ ПРИ КОЛОРЕКТАЛЬНОМ РАКЕA LINK BETWEEN AUTOPHAGY REGULATORY PROTEINS M-TOR AND BECLIN-1 AND PARAMETERS OF LYMPHOGENIC METASTASIS IN COLORECTAL CANCERhttps://orcid.org/0000-0002-1195-4008ВторушинС. В.VtorushinS. V.

Россия, 634050, г. Томск, Московский тракт, 2

доктор медицинских наук, доцент, профессор кафедры патологической анатомии, заведующий патологоанатомическим отделением, ФГБОУ ВО «Сибирский государственный  медицинский университет» Минздрава России

SPIN-код: 2442-4720. Researcher ID: S-3789-2016

2, Moskovsky Trakt, 634050-Tomsk, Russia

MD, Professor, Pathological Anatomy Department, Head of Pathological Anatomy Division, Siberian State Medical University (Tomsk, Russia)

Researcher ID: S-3789-2016

РачковскийК. В.RachkovskyK. V.

Россия, 634050, г. Томск, Московский тракт, 2

аспирант кафедры патологической анатомии, ФГБОУ ВО «Сибирский государственныймедицинский университет» Минздрава России 

SPIN-код: 6814-7094

2, Moskovsky Trakt, 634050-Tomsk, Russia

postgraduate, Pathological Anatomy Department, Siberian State Medical University

https://orcid.org/0000-0002-1909-1681КрахмальН. В.KrakhmalN. V.

Россия, 634050, г. Томск, Московский тракт, 2

кандидат медицинских наук, доцент кафедры патологической анатомии, ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава России

SPIN-код: 1543-6546. Researcher ID: S-3799-2016

2, Moskovsky Trakt, 634050-Tomsk, Russia

MD, PhD, Pathological Anatomy Department, Siberian State Medical University (Tomsk, Russia)

Researcher ID: S-3799-2016

https://orcid.org/0000-0002-8543-6027СтепановИ. В.StepanovI. V.

Россия, 634050, г. Томск, Московский тракт, 2

кандидат медицинских наук, доцент кафедры патологической анатомии, ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава России (г. Томск, Россия)

SPIN-код: 5930-3160. Researcher ID: C-8572-2012

2, Moskovsky Trakt, 634050-Tomsk, Russia

MD, PhD, Pathological Anatomy Department, Siberian State Medical University (Tomsk, Russia)

Researcher ID: C-8572-2012

https://orcid.org/0000-0001-9429-9813ЗавьяловаМ. В.ZavyalovaM. V.

Россия, 634050, г. Томск, Московский тракт, 2

доктор медицинских наук, профессор, заведующая кафедрой патологической анатомии, ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава России 

SPIN-код: 1229-0323. Researcher ID: C-8580-2012

2, Moskovsky Trakt, 634050-Tomsk, Russia

MD, Professor, Head of Pathological Anatomy Department, Siberian State Medical University

Researcher ID: C-8580-2012

zavyalovamv@mail.ruФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава РоссииРоссияSiberian State Medical UniversityRussian Federation2018020920181744147Copyright © Вторушин С.В., Рачковский К.В., Крахмаль Н.В., Степанов И.В., Завьялова М.В., 20182018Вторушин С.В., Рачковский К.В., Крахмаль Н.В., Степанов И.В., Завьялова М.В.Vtorushin S.V., Rachkovsky K.V., Krakhmal N.V., Stepanov I.V., Zavyalova M.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/814

На сегодняшний день влияние процессов аутофагии на канцерогенез остается не до конца изученным. С  одной стороны, аутофагия является опухолевым супрессором за счет активации разрушения онкогенных  протеинов, токсичных белков и дефектных органелл, которые могут обладать агрессивными свойствами и  способствовать повреждению ДНК клетки. C другой стороны, аутофагия может способствовать выживанию  опухолевых клеток в условиях гипоксии и присутствия активных форм кислорода, что происходит  преимущественно за счет блокировки механизмов апоптоза, увеличивая шансы на поддержание циркуляции  опухолевого клона. Регуляция аутофагии является сложным, многоэтапным и комплексным  процессом. Основным его регулятором является сигнальный путь, который активирует белок  протеинкиназосерин-треониновой специфичности m-Tor (мишень рапамицина у млекопитающих). В  литературе имеются данные о влиянии белков аутофагии ATG5, LC3A и LC3B, Beclin-1 на способность  злокачественно трансформированных клеток к выживанию, а также на развитие опухоли и ее прогрессирование. Крайне актуальными являются исследования, направленные на поиск возможных взаимосвязей между процессами аутофагии и патогенетическими механизмами канцерогенеза.

Цель исследования – изучить взаимосвязь экспрессионных параметров белков-регуляторов аутофагии m-TOR и Beclin-1 с параметрами лимфогенного метастазирования при колоректальном раке.

Материал и методы

Материал и методы. В исследование были включены 105 пациентов с колоректальным раком T1–4N0–3M0,находившихся на лечении в отделении торако-абдоминальной онкологии НИИ онкологии Томского НИМЦ в  период с 2012 по 2015 г. Средний возраст больных составил 59,7±4,3 года. Морфологическая верификация  диагноза колоректального рака проводилась на биопсийном материале фрагментов ткани первичной  опухоли. Распространенность онкологического заболевания определялась согласно международной классификации по системе TNM (2002).

Результаты

Результаты. Анализ частоты лимфогенного метастазирования в зависимости от наличия или отсутствия  экспрессии белков m-Tor и Beclin-1 в цитоплазме опухолевых клеток выявил статистически значимую связь между этими параметрами.

Заключение

Заключение. Полученные данные отчетливо демонстрируют тот факт, что снижение или утрата активности  процессов аутофагии в опухоли сопровождается реализацией механизмов лимфогенной диссеминации, которая является предиктором неблагоприятного прогноза заболевания.

Currently the impact of autophagy on carcinogenesis remains understudied. On the one hand, autophagy acts as a tumor suppressor, as it activates degradation of oncoproteins,  toxic proteins, and damaged cell organelles, that may be aggressive and lead to DNA  damage. On the other hand, autophagy may promote tumor cell survival under hypoxia and  in the presence of reactive oxygen species, which occurs primarily due to blocking of  apoptosis mechanisms, raising the chances for maintaining tumor clone dynamics.  Autophagy regulation is a complicated and multi-stage process. The main regulator here is a  signaling pathway that activates serine/threonine protein kinase m-TOR (the mammalian  target of rapamycin). Data on the impact of autophagic proteins ATG5, LC3A, LC3B, and  Beclin-1 on malignant cell survival as well as on tumor growth and progression have been  reported in literature. However, studies aimed at seeking possible relationships between autophagy and pathogenetic mechanisms of carcinogenesis are of great interest.

The aim of the study is to investigate a relationship between the expression parameters of  autophagy regulatory proteins m-TOR and Beclin-1 and the features of lymphogenic metastasis in colorectal cancer.

Materials and methods

Materials and methods. The study included 105 patients with T1-4N0-3M0 colorectal cancer treated in the Thoracic and Abdominal Department of Cancer Research Institute of  Tomsk Research Medical Center from 2012 to 2015. The average age of patients was  59.7±4.3 years. Morphological verification of the diagnosis was performed on the biopsy  samples of primary tumor tissue. Staging of colorectal cancer was determined according to  the TNM classification of malignant tumors (2002).

Results

Results. Analysis of the frequency of lymphogenic metastasis depending on the presence or absence of m-Tor and Beclin-1 expression in tumor cell cytoplasm revealed a statistically significant link between these variables.

Conclusion

Conclusion. The obtained findings clearly exhibit that deceleration or loss of autophagic  activity in the tumor is accompanied by implementation of lymphogenic dissemination, which is a predictor of an unfavorable outcome of the disease.

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