Regulation of apoptosis is impaired in atrophic gastritis associated with gastric cancer

Abstract

BackgroundGastric premalignant conditions, atrophic gastritis (AG) and intestinal metaplasia (IM) are characterized by an increase of proliferation and a reduction of apoptosis in epithelial cells. The epithelial cell kinetics in AG and IM in gastric mucosa adjacent to gastric cancer is still unclear. The aim of this study was to evaluate the epithelial cell turnover and expression of proliferation and apoptosis-related genes in gastric cancer (GC) and adjacent mucosa with atrophic gastritis or intestinal metaplasia (AG/IM GC+), as well as in atrophic gastritis or intestinal metaplasia mucosa of patients without GC (AG/IM GC-) and in control biopsy samples of non-transformed gastric mucosa (Control).MethodsWe selected 58 patients (M: F = 34:24; age range 20-84 years, median 61.06 years) with 4 well defined histological conditions: 20 controls with histological finding of non-transformed gastric mucosa, 20 patients with AG or IM (AG/IM GC-), and 18 patients with intestinal type gastric adenocarcinoma (GC) and AG or IM in the adjacent mucosa (3 cm from the macroscopic tumour margin, AG/IM GC+). We performed an immunohistochemical staining of Ki67 and TUNEL and quantitative RT-PCR to determine the expression of PCNA and Bax/Bcl-2.ResultsThe immunohistochemical expression of Ki67 and TUNEL in AG/IM GC- was significantly increased compared to not transformed gastric mucosa (p < 0.0001) but not compared to AG/IM in gastric mucosa adjacent to GC. Levels of Bcl-2 were reduced in GC and AG/IM GC- compared to controls as well as in AG/IM GC- compared to AG/IM in mucosa adjacent to GC+ (p < 0.05). Proliferation and apoptosis markers did not correlate with H.pylori status in our study population.ConclusionsIn AG/IM associated with GC, no significant changes in the epithelial cell turnover were detected. Decreased Bcl-2 gene expression signified atrophic gastritis and IM in presence of cancer, as well as intestinal type gastric adenocarcinoma.

Mechanism of E Lian Granule Reversing Chronic Atrophic Gastritis With Intestinal Metaplasia Based on Integrated Pharmacology and&nbsp;GEO Gene Chip

“…The low expression of the Bcl-2 gene suggests atrophic gastritis, IM, and intestinal-type gastric adenocarcinoma. 45 In terms of the molecular mechanism of cAMP and cGMP, team 42 of Zhang Jingren (one of the masters of TCM in China) detected plasma cAMP and cGMP in 87 cases of atrophic gastritis with spleen qi de ciency syndrome. The two indexes of all patients were found to be lower than the normal low limit.…”

Integrating Network Pharmacology and Experimental Validation to Investigate the Mechanisms of Huazhuojiedu Decoction to Treat Chronic Atrophic Gastritis

“…An increase in proliferation and reduction in apoptosis in epithelial cells were the characteristics of atrophic gastritis (AG) and IM. Apoptosis was increased in chronic gastritis and decreased when chronic gastritis progressed to IM or AG [ 29 ]. During H. pylori infection, the gastric fovea epithelium and glands in the lamina propria are destroyed by direct bacterial toxicity and inflammation.…”

Effect and mechanism of Acoritataninowii Rhizoma and Curcumae Radix on chronic gastritis: a network pharmacology study

“…With deepening researches, a sustained in ammatory reaction and abnormal apoptosis of gastric mucosa are con rmed as important causes in the pathogenesis of chronic atrophic gastritis, which have drawn growing attention [31,32] . An impaired balance between proliferation and apoptosis was detected in gastric cancer and in atrophic gastritis or intestinal metaplasia in gastric mucosa adjacent to cancer [33] .…”