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H. pylori Infection Is Associated with DNA Damage of Lgr5-Positive Epithelial Stem Cells in the Stomach of Patients with Gastric Cancer

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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.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, Founders 6, Philadelphia, PA, 19104, USA

    Takeshi Uehara, Deqin Ma, Yuan Yao, Amy Ziober, Michael Feldman & Antonia R. Sepulveda

  2. Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan

    Takeshi Uehara & Hiroyoshi Ota

  3. Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    John P. Lynch

  4. Department of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Knashawn Morales

Authors
  1. Takeshi Uehara
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  2. Deqin Ma
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  3. Yuan Yao
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  4. John P. Lynch
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  5. Knashawn Morales
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  6. Amy Ziober
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  7. Michael Feldman
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  8. Hiroyoshi Ota
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  9. Antonia R. Sepulveda
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Correspondence to Antonia R. Sepulveda.

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Uehara, T., Ma, D., Yao, Y. et al. H. pylori Infection Is Associated with DNA Damage of Lgr5-Positive Epithelial Stem Cells in the Stomach of Patients with Gastric Cancer. Dig Dis Sci 58, 140–149 (2013). https://doi.org/10.1007/s10620-012-2360-8

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  • DOI: https://doi.org/10.1007/s10620-012-2360-8

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