Сharacterization of the immune microenvironment's cellular composition and its influence on gene expression during metaplastic changes of the gastric mucosa epithelium

Abstract

Rationale. Intestinal metaplasia of gastric mucosa epithelium in chronic atrophic gastritis is considered by most authors as a precancerous condition, but it is potentially reversible. The study of the regulation mechanisms of metaplastic epithelial changes development may become the key in understanding the process of carcinogenesis and prevention of cancer development. Objective. To determine whether there is a relationship between microenvironment and development of metaplasia of gastric mucosa epithelium of patients with chronic atrophic gastritis by assessing gene expression and cellular composition of immune infiltrate. Materials and Methods. A retrospective cohort study, the alternative hypothesis of which is that the composition of the gastric mucosa immune microenvironment differs between cases with and without metaplastic changes in the epithelium. Biopsy specimens of the mucosa (n = 38) obtained during endoscopic examination from five sites (2 from the antrum, 2 from the body, 1 from the corner) of the stomach of patients with chronic atrophic gastritis of unspecified etiology, as well as the results of RNA sequencing isolated from biopsy specimens of patients with chronic gastritis obtained from the NCBI open database (n = 12) served as the material for the study. Histological, histochemical staining methods, immunohistochemical study were applied during the study. Morphometric, statistical and bioinformatic analyses were performed. Results. It was found that the proportion of macrophages, T-cytotoxic lymphocytes and plasmocytes was increased in the samples with metaplastic changes of the gastric mucosa epithelium. A correlation between T-cytotoxic lymphocytes and the chance of metaplasia development was found. It was found that changes in the number of T-helper cells, T-cytotoxic lymphocytes, T-regulatory cells and plasmocytes are associated with changes in the expression of five 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 microenvironment may be their influence on gene expression as an epigenetic factor.