Journal article
H. pylori infection is associated with DNA damage of Lgr5-positive epithelial stem cells in the stomach of patients with gastric cancer
Digestive diseases and sciences, Vol.58(1), pp.140-149
01/2013
DOI: 10.1007/s10620-012-2360-8
PMCID: PMC3816997
PMID: 22945475
Abstract
Background: H. pylori (Hp) infection is a major risk factor in gastric carcinogenesis leading to epithelial mutagenesis, and may affect gastric epithelial stem cells.
Aims: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Details
- Title: Subtitle
- H. pylori infection is associated with DNA damage of Lgr5-positive epithelial stem cells in the stomach of patients with gastric cancer
- Creators
- Takeshi Uehara - Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USADeqin Ma - Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USAYuan Yao - Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USAJohn P Lynch - Department of Medicine, Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, PA, USAKnashawn Morales - Department of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PAAmy Ziober - Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USAMichael Feldman - Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USAHiroyoshi Ota - Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, JapanAntonia R Sepulveda - Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
- Resource Type
- Journal article
- Publication Details
- Digestive diseases and sciences, Vol.58(1), pp.140-149
- DOI
- 10.1007/s10620-012-2360-8
- PMID
- 22945475
- PMCID
- PMC3816997
- NLM abbreviation
- Dig Dis Sci
- ISSN
- 0163-2116
- eISSN
- 1573-2568
- Grant note
- U54 CA163004 || CA / National Cancer Institute : NCI U01 DK085551 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
- Language
- English
- Date published
- 01/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984047615202771
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