MorphologyMorphologyМорфология1026-35432949-2556Eco-Vector63035010.17816/morph.630350Original Study ArticlesОригинальные исследованияResearch ArticleСharacterization of the immune microenvironment’s cellular composition and its influence on gene expression during metaplastic changes of the gastric mucosa epitheliumХарактеристика клеточного состава иммунного микроокружения и его влияния на экспрессию генов при метапластических изменениях эпителия слизистой оболочки желудкаhttps://orcid.org/0000-0003-3498-45735430-7130SlepovIurii K.СлеповЮрий Константинович
Russian Federation
slepovurij95@gmail.comhttps://orcid.org/0000-0003-4109-01055605-1140EmelinAleksey M.ЕмелинАлексей Михайлович
Russian Federation
eamar40rn@gmail.comhttps://orcid.org/0000-0001-8389-38412957-1687DeevRoman V.ДеевРоман Вадимович
Russian Federation

MD, Cand. Sci. (Medicine), Assistant Professor

канд. мед. наук, доцент

romdey@gmail.comNorth-Western State Medical University named after I.I. MechnikovСеверо-Западный государственный медицинский университет имени И.И. МечниковаPetrovsky National Research Centre of SurgeryРоссийский научный центр хирургии имени академика Б.В. Петровского1706202415102023161453651504202424052024Copyright ©; 2023, Eco-VectorCopyright ©; 2023, Эко-ВекторCopyright ©; 2023,2023Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0/https://j-morphology.com/1026-3543/article/view/630350

BACKGROUND: Intestinal metaplasia of the gastric mucosa epithelium in chronic atrophic gastritis is considered a precancerous condition; however, it is potentially reversible. The study of the regulation mechanisms of metaplastic epithelial changes may help in understanding carcinogenesis and cancer prevention.

AIM: To determine whether the microenvironment is related to the development of gastric mucosa epithelium metaplasia in patients with chronic atrophic gastritis by assessing gene expression and cellular composition of immune infiltrates.

MATERIALS AND METHODS: In this retrospective cohort study, the alternative hypothesis was that the composition of the immune microenvironment of the gastric mucosa differed between cases with and without metaplastic changes in the epithelium. Biopsy specimens of the mucosa (n=38) obtained during endoscopic examination from five stomach sites (2 from the antrum, 2 from the body, and 1 from the corner) in patients with chronic atrophic gastritis of unspecified etiology and results of RNA sequencing of biopsy specimens of patients with chronic gastritis registered in the NCBI open database (n=12) were analyzed. Histological analysis, histochemical staining methods, and immunohistochemical study and morphometric, statistical, and bioinformatic analyses were performed.

RESULTS: The proportion of macrophages, T-cytotoxic lymphocytes, and plasmocytes increased in the samples with metaplastic changes of the gastric mucosa epithelium. A correlation was found between T-cytotoxic lymphocytes and risk for metaplasia. It was found that changes in the number of B cells, macrophages M2, T-regulatory cells and NK-cells are associated with increase in the expression of six genes most specific for intestinal-type epithelium.

CONCLUSION: The significant difference in the composition of the immune microenvironment between samples with and without metaplastic changes in the mucosal epithelium indicates the potential influence of immune cells on the development of metaplasia and progression of the pathological process along the Correa cascade. One of the mechanisms of regulation of metaplasia development by the microenvironment may be their influence on gene expression as an epigenetic factor.

Обоснование. Кишечная метаплазия эпителия слизистой оболочки желудка при хроническом атрофическом гастрите большинством авторов рассматривается как предраковое состояние, но при этом является потенциально обратимой. Изучение механизмов регуляции развития метапластических изменений эпителия может стать ключевым в понимании процесса канцерогенеза и профилактике развития рака.

Цель исследования — установить наличие или отсутствие взаимосвязи между микроокружением и развитием метаплазии эпителия слизистой оболочки желудка больных хроническим атрофическим гастритом путём оценки экспрессии генов и клеточного состава иммунного инфильтрата.

Материалы и методы. Проведено ретроспективное когортное исследование, альтернативной гипотезой которого является предположение о том, что состав иммунного микроокружения слизистой оболочки желудка различается в случаях с наличием и отсутствием метапластических изменений эпителия. Материалом для исследования послужили биоптаты слизистой оболочки (n=38), полученные при эндоскопическом исследовании из пяти участков (2 из привратниковой пещеры, 2 из тела желудка, 1 из угловой вырезки) желудка у пациентов с хроническим атрофическим гастритом неуточнённой этиологии; а также результаты секвенирования РНК, выделенной из биоптатов больных хроническим гастритом, которые были получены из открытой базы данных NCBI (n=12). В ходе работы применяли гистологический, гистохимический методы окрашивания, проводили иммуногистохимическое исследование, морфометрический, статистический и биоинформатический анализ.

Результаты. Установлено, что в образцах с метапластическими изменениями эпителия слизистой оболочки желудка увеличена доля макрофагов, Т-цитотоксических лимфоцитов и плазмоцитов. Обнаружена взаимосвязь Т-цитотоксических лимфоцитов и шанса развития метаплазии. Установлено, что изменение количества B-лимфоцитов, макрофагов фенотипа М2, Т-регуляторных лимфоцитов и NK-клеток ассоциировано с увеличением экспрессии шести генов, наиболее специфичных для эпителия кишечного типа.

Заключение. Значительная разница в составе иммунного микроокружения между образцами с метапластическими изменениями эпителия слизистой оболочки и без них указывает на потенциальное влияние клеток иммунитета на развитие метаплазии и прогрессирование патологического процесса по каскаду Корреа. Одним из механизмов регуляции развития метаплазии микроокружением может являться его влияние на экспрессию генов как эпигенетического фактора.

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