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. 2017 Dec 14;9(3):3936-3945.
doi: 10.18632/oncotarget.23278. eCollection 2018 Jan 9.

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

Osamu Toyoshima  1 , Chizu Tanikawa  2 , Ryuta Yamamoto  2   3 , Hidenobu Watanabe  4 , Hiroharu Yamashita  3   1 , Kosuke Sakitani  5   1 , Shuntaro Yoshida  5   1 , Michiaki Kubo  6 , Keitaro Matsuo  7 , Hidemi Ito  7 , Kazuhiko Koike  5 , Yasuyuki Seto  3 , Koichi Matsuda  2   8
Affiliations

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

Osamu Toyoshima et al. Oncotarget. .

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 PSCA expression by host genetic variation and bacterial infection might contribute to gastritis progression after H. pylori infection.

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

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Scheme of SNP rs2294008 contribution to the diseases related with H. pylori infection including gastritis, gastric cancer, and duodenal ulcer
Figure 2
Figure 2. The suppression of PSCA expression by H. pylori infection
Box-plots with medians for PSCA expression normalized to ACTB in biopsy samples of gastric mucosa. (A) PSCA mRNA in H. pylori-negative controls (n = 28), in H. pylori-infected patients (n = 280), in H. pylori-infected mild gastritis patients (n = 110), or in H. pylori-infected severe gastritis patients (n = 168). The P values were calculated by a Mann-Whitney U test. (B) The comparison of the expression levels of PSCA in each individual patient (n = 133) before and after H. pylori eradication. The P value was calculated by a Wilcoxon signed rank test.
Figure 3
Figure 3. The association of SNP rs2294008 with PSCA expression
Box-plots with medians for PSCA expression normalized to ACTB in biopsy samples of gastric mucosa. The P values were calculated by a Kruskal-Wallis test. (A) PSCA mRNA in H. pylori-negative controls (n = 28), (B) in H. pylori-infected patients (n = 280), (C) in H. pylori-infected mild gastritis patients (n = 110), (D) and in H. pylori-infected severe gastritis patients (n = 168).
Figure 4
Figure 4. Fold PSCA mRNA induction by H. pylori eradication
Box-plots with medians fold induction of PSCA expression normalized to ACTB. The fold induction was defined as PSCA expression after eradication divided by PSCA expression before eradication using paired samples. PSCA mRNA levels in paired samples before and after H. pylori eradication are quantified by the qRT-PCR analysis (CC; n = 15, CT; n = 57, TT; n = 61). The P values were calculated by a Kruskal-Wallis test.
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