Oncotarget

Research Papers:

Decrease in PSCA expression caused by Helicobacter pylori infection may promote progression to severe gastritis

Osamu Toyoshima, Chizu Tanikawa, Ryuta Yamamoto, Hidenobu Watanabe, Hiroharu Yamashita, Kosuke Sakitani, Shuntaro Yoshida, Michiaki Kubo, Keitaro Matsuo, Hidemi Ito, Kazuhiko Koike, Yasuyuki Seto and Koichi Matsuda _

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Oncotarget. 2018; 9:3936-3945. https://doi.org/10.18632/oncotarget.23278

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Abstract

Osamu Toyoshima1, Chizu Tanikawa2, Ryuta Yamamoto2,3, Hidenobu Watanabe4, Hiroharu Yamashita3,1, Kosuke Sakitani5,1, Shuntaro Yoshida5,1, Michiaki Kubo6, Keitaro Matsuo7, Hidemi Ito7, Kazuhiko Koike5, Yasuyuki Seto3 and Koichi Matsuda2,8

1Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan

2Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

3Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4Pathology and Cytology Laboratories (PCL) Japan, Tokyo, Japan

5Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

6Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan

7Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan

8Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan

Correspondence to:

Koichi Matsuda, email: [email protected]

Keywords: genetic polymorphism; gene regulation; H. pylori infection; gastric cancer; Gastritis

Received: September 19, 2017     Accepted: December 03, 2017     Published: December 14, 2017

ABSTRACT

SNP rs2294008 in Prostate Stem Cell Antigen (PSCA) and decreased PSCA expression are associated with gastric cancer. The objective of this study is to investigate the role of rs2294008 and PSCA expression in the gastritis-gastric cancer carcinogenic pathway. We conducted a case-control association study of H. pylori-infected gastritis and gastric cancer. rs2294008 was associated with the progression to chronic active gastritis (P = 9.4 × 10–5; odds ratio = 3.88, TT + TC vs CC genotype), but not with H. pylori infection per se nor with the progression from active gastritis to gastric cancer. We also assessed the association of rs2294008 with PSCA mRNA expression in the gastric mucosa at various disease stages and found that rs2294008 was associated with PSCA expression (P = 1.3 × 10–12). H. pylori infection (P = 5.1 × 10–8) and eradication therapy (P < 1 × 10–11) resulted in the reduced and increased PSCA expression, respectively, indicating negative regulation of PSCA expression by H. pylori infection. PSCA expression was decreased in severe gastritis compared with mild gastritis only among T allele carriers. Our findings revealed the regulation of PSCAexpression by host genetic variation and bacterial infection might contribute to gastritis progression after H. pylori infection.


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