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

Abstract

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.