Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press51210.17650/2313-805X-2023-10-1-49-56RESEARCH ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИMicroRNA expression profile in isolated circulating tumor cells in colorectal cancerПрофиль экспрессии микроРНК в изолированных циркулирующих опухолевых клетках при колоректальном ракеhttps://orcid.org/0000-0003-3061-6108KitO. I.КитО. И.
Russian Federation

63 14 th Line, Rostov-on-Don 344037

344037 Ростов-на-Дону, 14-я линия, 63

https://orcid.org/0000-0002-6496-9641NovikovaI. A.НовиковаИ. А.
Russian Federation

63 14 th Line, Rostov-on-Don 344037

344037 Ростов-на-Дону, 14-я линия, 63

https://orcid.org/0000-0001-6358-7361TimoshkinaN. N.ТимошкинаН. Н.
Russian Federation

63 14 th Line, Rostov-on-Don 344037

344037 Ростов-на-Дону, 14-я линия, 63

https://orcid.org/0000-0001-8633-2660GvaldinD. Yu.ГвалдинД. Ю.
Russian Federation

63 14 th Line, Rostov-on-Don 344037

344037 Ростов-на-Дону, 14-я линия, 63

https://orcid.org/0000-0003-2385-6285PushkinA. A.ПушкинА. А.
Russian Federation

Anton Andreevich Pushkin

63 14 th Line, Rostov-on-Don 344037

Антон Андреевич Пушкин

344037 Ростов-на-Дону, 14-я линия, 63

anton.a.pushkin@gmail.comKaimakchiO. Yu.КаймакчиО. Ю.
Russian Federation

29 Nahichevanskij pereulok, Rostov-on-Don 344022

344022 Ростов-на-Дону, Нахичеванский пер., 29

https://orcid.org/0000-0001-7328-8074MaslovA. A.МасловА. А.
Russian Federation

63 14 th Line, Rostov-on-Don 344037

344037 Ростов-на-Дону, 14-я линия, 63

https://orcid.org/0000-0001-6881-2281ShaposhnikovA. V.ШапошниковА. В.
Russian Federation

63 14 th Line, Rostov-on-Don 344037

344037 Ростов-на-Дону, 14-я линия, 63

National Medical Research Center for Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии» Минздрава РоссииRostov State Medical University, Ministry of Health of RussiaФГБОУ ВО «Ростовский государственный медицинский университет» Минздрава России1501202310149563103202331032023Copyright ©; 2023, Kit O.I., Novikova I.A., Timoshkina N.N., Gvaldin D.Y., Pushkin A.A., Kaimakchi O.Y., Maslov A.A., Shaposhnikov A.V.Copyright ©; 2023, Кит О.И., Новикова И.А., Тимошкина Н.Н., Гвалдин Д.Ю., Пушкин А.А., Каймакчи О.Ю., Маслов А.А., Шапошников А.В.2023Kit O.I., Novikova I.A., Timoshkina N.N., Gvaldin D.Y., Pushkin A.A., Kaimakchi O.Y., Maslov A.A., Shaposhnikov A.V.Кит О.И., Новикова И.А., Тимошкина Н.Н., Гвалдин Д.Ю., Пушкин А.А., Каймакчи О.Ю., Маслов А.А., Шапошников А.В.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/512

Introduction. Colorectal cancer is a frequently diagnosed disease being in the third place among oncological diseases both in incidence and mortality. Currently, researchers focus on development of more accessible and reliable biomarkers of colorectal cancer to overcome the problems in diagnosis and progression prognosis of this pathology.

Aim. To investigate characteristics of microRNA expression in circulating tumor cells (CTC) of patients with colorectal cancer. Materials and methods. The study included blood samples from 299 patients with colon cancer, stages II (T3–4N0M0), III (T1–4N1–2M0) and IV (T1–4N0–2M1). Circulating tumor cells were identified using EpCAM marker detection system. Relative expression of hsa-let-7i-5p, hsa-miR-126-5p, hsa-miR-143-3p, hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-26a-5p, hsa-miR-92a-3p micro RNA in CTC was measured using polymerase chain reaction.

Results. Positive CTC status was observed in 188 (62.9 %) of 299 patients, negative in 111 (37.1 %). In the patient group with pT1–2 tumors, the majority of patients did not have CTC (53.3 %). In other patients with pT1–2 disease, the number of CTC was 1.2 and 4.4 times lower than in patients with pT3 and pT4 disease, respectively. In pT4, 1–3 CTC were found 2.7 and 1.7 times more frequently, 3 CTC 1.4 times more frequently than in pT1–2 and pT3, respectively (p ≤0.05). Presence of metastatic lesions increases the probability of CTC detection by the factor of 2.1: in metastases, >3 CTC were observed 60.1 times more frequently than in M0 (p ≤0.05). Expression of hsa-miR-143-3p and hsa-miR-26a-5p microRNA in CTC of patients with stage III colorectal cancer was respectively 2.5 and 5 times lower than in patients with stage II disease (p <0.05) and expression of hsa-miR-21-5p and hsa-miR-92a-3p microRNA was respectively 3.2 and 3 times higher (p <0.05). In CTC of patients with stage IV colorectal cancer, the relative level of expression of hsa-miR-143-3p and hsa-miR-26a-5p was respectively 4.6 and 5.3 times lower (p <0.05) compared to the level of expression in stage II disease, and hsa-miR-126-5p, hsa-miR-21-5p, hsa-miR-25-3p and hsa-miR-92a-3p expression levels were respectively 2.6, 4.6, 2.6 and 5.0 times higher (p<0.05) (statistically significant results).

Conclusion. The level of microRNA expression in CTC can be used for differential diagnosis of regional and distant metastases.

Введение. Колоректальный рак – часто диагностируемое заболевание, занимающее 3-е место среди онкологических заболеваний как по частоте встречаемости, так и по смертности. Сегодня внимание исследователей сосредоточено на разработке более доступных и надежных биомаркеров колоректального рака для преодоления ограничений в диагностике и прогнозе течения данной патологии.

Цель исследования – изучение особенностей экспрессии микроРНК в циркулирующих опухолевых клетках (ЦОК) пациентов с колоректальным раком.

Материалы и методы. В исследование включены образцы крови от 299 больных раком ободочной кишки II (T3–4N0M0), III (T1–4N1–2M0) и IV (T1–4N0–2M1) стадий. Циркулирующие опухолевые клетки были отобраны с помощью системы детекции маркера EpCAM. Методом полимеразной цепной реакции исследована относительная экспрессия микроРНК hsa-let-7i-5p, hsa-miR-126-5p, hsa-miR-143-3p, hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-26a-5p, hsa-miR-92a-3p в ЦОК.

Результаты. Положительный статус ЦОК выявлен у 188 (62,9 %) из 299 больных, отрицательный – у 111 (37,1 %). В группе больных с опухолями pT1–2 преобладали пациенты, у которых не были обнаружены ЦОК (53,3 %). У остальных пациентов с заболеванием pT1–2 ЦОК оказалось в 1,2 и 4,4 раза меньше, чем у пациентов с заболеванием pT3 и pT4 соответственно. При pT4 1–3 ЦОК встречались в 2,7 и 1,7 раза, а 3 ЦОК – в 1,4 раза чаще по сравнению с pT1–2 и pT3 соответственно (p ≤0,05). Наличие метастатического поражения в 2,1 раза повышает вероятность выявления ЦОК: при метастазах >3 ЦОК обнаруживаются в 60,1 раза чаще, чем при M0 (p ≤0,05). Экспрессия микроРНК hsa-miR-143-3p и hsa-miR-26a-5p в ЦОК у пациентов с колоректальным раком III стадии была ниже, чем у пациентов с заболеванием II стадии, в 2,5 и 5 раз (p <0,05) соответственно, а экспрессия hsa-miR-21-5p и hsa-miR-92a-3p – выше в 3,2 и 3 раза (p <0,05) соответственно. В ЦОК больных колоректальным раком IV стадии уровень относительной экспрессии hsa-miR-143-3p и hsa-miR-26a-5p оказался ниже в 4,6 и 5,3 раза соответственно (p <0,05) по сравнению с уровнем экспрессии при заболевании II стадии, а уровень экспрессии hsa-miR-126-5p, hsa-miR-21-5p, hsa-miR25-3p и hsa-miR-92a-3p – выше в 2,6; 4,6; 2,6 и 5,0 раз соответственно (p <0,05) (результаты статистически значимы).

Заключение. Уровень экспрессии микроРНК в ЦОК может быть использован для дифференциальной диагностики наличия регионарных и отдаленных метастазов.

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