H. pylori infection is associated with DNA damage of Lgr5-positive epithelial stem cells in the stomach of patients with gastric cancer.

Abstract

H. pylori (Hp) infection is a major risk factor in gastric carcinogenesis leading to epithelial mutagenesis, and may affect gastric epithelial stem cells. To characterize the expression of Lgr5, a marker of epithelial stem cells in human gastric mucosa, to determine whether Hp infection affects Lgr5-positive epithelial cells (LPECs) and whether LPECs are susceptible to DNA damage associated with Hp infection. Lgr5 expression was characterized in non-neoplastic gastric mucosa from 52 patients (34 with and 18 without gastric cancer (GC); 21 Hp-positive (Hp+) and 31 Hp-negative (Hp-)) by immunohistochemical and immunofluorescence staining. To determine the extent of DNA damage in LPECs, nuclear 8-hydroxydeoxyguanosine (8OHdG), a marker of DNA damage associated with oxidative stress, was measured by quantitative spectral image analysis. LPECs were primarily present in gastric antrum. Higher numbers of LPECs were seen in Hp+than in Hp- non-neoplastic mucosa of GC patients, P=.006, but not in patients without GC. 8OHdG levels in LPECs were significantly higher than in Lgr5-negative epithelial cells in Hp+GC patients (P=.012) but not in Hp- cases (P=.414), whereas no difference was seen between Hp+ and Hp- mucosa of patients without GC. The Lgr5-positive epithelial stem cell pool is expanded in Hp-associated gastritis in the antrum of patients with GC. In GC patients with active Hp infection, LPECs may be more susceptible to DNA damage than Lgr5-negative epithelial cells, suggesting that Hp infection may contribute to GC risk by affecting epithelial stem cells in the human stomach.