Helicobacter pylori Infection Facilitates the Expression of Resistin-like Molecule Beta in Gastric Carcinoma and Precursor Lesions

Abstract

Helicobacter pylori (H. pylori) was reported to be associated with gastric carcinogenesis. Resistin-like molecule beta (RELMβ), a recently described goblet cell-specific protein, was demonstrated to aberrantly express in gastric cancer and correlated with its clinicopathological features. This study aimed to examine the association between H. pylori and RELMβ expression in gastric carcinoma and precursor lesions. H. pylori infection and RELMβ expression were immunohistochemically evaluated in gastric biopsies from 230 patients. The biopsies consisted of normal gastric mucosa (n=20), mucosa with chronic gastritis (n=41), intestinal metaplasia (n=42), dysplasia (n=31), intestinal-type adenocarcinoma (n=56), and diffuse-type adenocarcinoma (n=40). RELMβ expression was measured in gastric biopsies after H. pylori eradication therapy in a subgroup of 32 patients. Cultured gastric cancer cell line SGC-7901 was infected with H. pylori strains, and RELMβ expression was detected by reverse transcription PCR, real-time PCR and Western blotting. Higher RELMβ immunoreactivity was observed in H. pylori-positive intestinal metaplasia (P=0.003), dysplasia (P=0.032), intestinal-type (P=0.037) and diffuse-type adenocarcinomas (P=0.001) than in H. pylori-negative specimens. Expression rates of RELMβ in dysplasia (P=0.005), intestinal-type adenocarcinoma (P<0.001), and diffuse-type adenocarcinoma (P=0.001) were significantly correlated with the grade of H. pylori density. In addition, H. pylori eradication reduced the RELMβ intensity in intestinal metaplasia (P=0.001). Infection of gastric cancer SGC-7901 cells with cag pathogenicity island (PAI)-positive H. pylori TN2, but not with its PAI totally deleted mutant (TN2-ΔPAI) for 4-8 h, resulted in enhanced protein and transcript levels of RELMβ (P<0.05). In summary, our study suggested that H. pylori infection facilitated the expression of RELMβ in gastric garcinoma and precursor lesions.

Keywords: Helicobacter pylori; gastric carcinoma; immunohistochemistry; resistin-like molecule beta.