rpmjResearch'n Practical Medicine JournalResearch and Practical Medicine Journal2410-1893"QUASAR", LLC10.17709/2410-1893-2021-8-2-2rpmj-719Research ArticleОригинальные статьи. Онкология, лучевая терапияOriginal Articles. ОncologyОсобенности экспрессии маркеров эпителиально-мезенхимального перехода – E-кадгерина и ZEB1 – при колоректальном ракеExpression of epithelial-mesenchymal transition markers E-cadherin and ZEB1 in colorectal cancerhttps://orcid.org/0000-0002-6496-9641НовиковаИ. А.NovikovaI. A.

Новикова Инна Арнольдовна – к.м.н., заместитель генерального директора по науке, SPIN: 4810-2424, AuthorID: 726229, ResearcherID: E-7710-2018, Scopus Author ID: 7005153343

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

Inna A. Novikova – Cand. Sci. (Med.), deputy General Director for Science, SPIN: 4810-2424, AuthorID: 726229, ResearcherID: E-7710-2018, Scopus Author ID: 7005153343

63 14 line str., Rostov-on-Don 344037

novikovainna@yahoo.comhttps://orcid.org/0000-0003-3061-6108КитО. И.KitO. I.

Кит Олег Иванович – член-корр. РАН, д.м.н., профессор, генеральный директор, SPIN: 1728-0329, AuthorID: 343182, ResearcherID: U-2241-2017, Scopus Author ID: 55994103100

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

Oleg I. Kit – corr. member of RAS, Dr. Sci. (Med.), professor, general director, SPIN: 1728-0329, AuthorID: 343182, ResearcherID: U-2241-2017, Scopus Author ID: 55994103100

63 14 line str., Rostov-on-Don 344037

ФГБУ «НМИЦ онкологии» Минздрава РоссииРоссияNational Medical Research Centre for Oncology of the Ministry of Health of RussiaRussian Federation202120062021822333Copyright © Новикова И.А., Кит О.И., 20212021Новикова И.А., Кит О.И.Novikova I.A., Kit O.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpmj.ru/rpmj/article/view/719Цель исследования

Цель исследования. Оценить особенности экспрессии маркеров эпителиально-мезенхимального перехода – E-кадгерина и ZEB1 у пациентов колоректальным раком (КРР) II-IV стадий.

Материалы и методы

Материалы и методы. Материалом для исследования послужил операционный материал 299 больных раком толстой кишки II-IV стадий, находившихся на лечении в ФГБУ «НМИЦ онкологии» Минздрава России с 2013 по 2016 гг. Больные находились в возрасте от 42 до 86 лет, где средний возраст составил 64,2±1,7 года. У 110 больных диагностирована II стадия заболевания (T3-4 N0 M0 ), у 88 больных – III стадия (T1-4 N1-2 M0 ), у 101 пациента – IV стадия (T1-4 N0-2 M1 ). Для иммуногистохимического исследования использовали поликлональные антитела к ZEB1 (фирмы Biorbyt Ltd., Великобритания) и моноклональные мышиные антитела к E-cadherin (фирмы Diagnostic BioSystems, США). Оценивали интенсивность и степень окрашивания опухолевых клеток, долю окрашенных опухолевых клеток в образце и количество пациентов с положительным и отрицательным статусом по экспрессии маркера. Сравнение групп проводили с помощью непараметрического критерия Манна-Уитни (U-критерий) и критерия χ² Пирсона.

Результаты

Результаты. Было выявлено, что положительная экспрессия E-кадгерина встречалась в 64,5 % (193 из 299 больных), ZEB1 наблюдалась у 80,6 % (241 из 299 больных). Количество пациентов с позитивными E-кадгерин опухолями статистически значимо уменьшалось (χ2 =15,888 при p<0,001) от II к IV стадии, тогда как в случае с ZEB1 – статистически значимо увеличивалось (χ²=43,912 при p><0,001) от II до IV стадии. Средние значения уровня экспрессии положительно окрашенных клеток составили: при II стадии – E-кадгерин – 55,3±6,8 %; ZEB1-43,0±5,9 %; при III стадии – E-кадгерин – 38,4±5,8 %; ZEB1-77,0±5,5 %; при IV стадии – E-кадгерин – 14,7±4,7 %; ZEB1-76,9±3,5 %. Выявлена достоверная разница средних значений экспрессии ZEB1 при III и IV стадиях в сравнении со II стадией, а также экспрессии E-кадгерина при II и III стадиях в сравнении с IV стадией (р><0,05). Значимых различий средних значений экспрессии ZEB1 и E-кадгерина не отмечено между III и IV стадиями, II и III стадиями, соответственно.

Заключение

Заключение. Таким образом, в исследовании удалось показать статистически значимую связь между стадиями опухолевого процесса, экспрессией E-кадгерина и ZEB1 при эпителиально-мезенхимальном переходе (ЭМП). Снижение экспрессии E-кадгерина опухолевыми клетками больных от II стадии к IV и усиление экспрессии ZEB1 в исследуемых группах оказались статистически значимы (р<0,05).

Purpose of the study

Purpose of the study. Evaluation of expression of the epithelial-mesenchymal transition markers E-cadherin and ZEB1 in patients with stage II-IV colorectal cancer (CRC).

Materials and methods

Materials and methods. The study included operational material obtained from 299 patients aged 42–86 years (mean age 64.2±1.7 years) with stage II-IV CRC treated at National Medical Research Centre for Oncology in 2013-2017. Stage II CRC (T3-4 N0 M0 ) was diagnosed in 110 patients, stage III (T1-4 N1-2 M0 ) – in 88 patients, stage IV (T1-4 N0-2 M1 ) – in 101 patients. Polyclonal rabbit antibodies to ZEB1 (Biorbyt Ltd., UK) and mouse monoclonal antibodies to E-cadherin (Diagnostic BioSystems, USA) were used for an IHC analysis. The intensity and degree of tumor cell staining, percentage of stained tumor cells in the sample and the number of patients with positive and negative marker expression were determined. Groups were compared using the Mann–Whitney U test and the Pearson's chi-square test.

Results

Results. Positive expression of E-cadherin was found in 64.5 % (193 of 299 patients), ZEB1 – in 80.6 % (241 of 299 patients). The number of patients with E-cadherin-positive tumors statistically significantly decreased (χ2 =15.888 at p<0.001) from stage II to stage IV, while for ZEB1, on the contrary, it statistically significantly increased (χ2 =43.912 at p><0.001) from stage II to stage IV. The mean values of expression in positively stained cells were: in stage II – E-cadherin 55.3±6.8 %, ZEB1 43.0±5.9 %; in stage III – E-cadherin 38.4±5.8 %, ZEB1 77.0±5.5 %; in stage IV – E-cadherin 14.7±4.7 %, ZEB1 76.9±3.5 %. Significant differences were observed between the mean values of ZEB1 expression in stages III and IV compared to stage II, as well as between the mean values of E-cadherin expression in stages II and III compared to stage IV (p><0.05). No significant differences were found in the mean values of ZEB1 and E-cadherin expression in stages III and IV, II and III respectively.

Conclusions

Conclusions. The study demonstrated statistically significant relationship between tumor stages and expression of E-cadherin and ZEB1 in the epithelial-mesenchymal transition. The loss of the E-cadherin expression in tumor cells of patients from stage II to stage IV and increased expression of ZEB1 in the studied groups were statistically significant (p<0.05).

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