Helicobacter pylori Eradication Downregulates Cellular Inhibitor of Apoptosis Protein 2 in Gastric Carcinogenesis

Gut Liver. 2017 Jan 15;11(1):79-86. doi: 10.5009/gnl15585.

Abstract

Background/aims: To evaluate the expression of cellular inhibitor of apoptosis protein 2 (cIAP2) during gastric carcinogenesis after Helicobacter pylori (HP) infection and after HP eradication.

Methods: We divided non-cancer patients into four groups according to the status of HP infection and atrophic gastritis (AG)/intestinal metaplasia (IM). We compared cIAP2 mRNA expression among these four groups and patients with HP-positive early gastric cancer (EGC) by using real-time polymerase chain reaction (PCR). We evaluated the expression of cIAP2 messenger RNA (mRNA)/protein by using real-time PCR/immunohistochemistry and the degree of apoptosis with a terminal deoxynucleotidyl transferasemediated nick end labeling assay before and 12 months after endoscopic submucosal dissection (ESD) in HP-positive EGC patients, regardless of whether they had undergone eradication therapy.

Results: The expression of cIAP2 mRNA was significantly higher in the groups with HP(+), AG/IM(+), and HP-positive EGC than in the control, HP(+), and AG/ IM(-) groups (p<0.005). In the HP eradication group, the expression of cIAP2 mRNA/protein significantly decreased (p=0.006) and apoptosis increased at the 12-month follow-up after ESD. In the HP noneradication group, the aforementioned changes were not found during the same follow-up period.

Conclusions: The expression of cIAP2 increased during gastric carcinogenesis after HP infection; HP eradication in the patients who had undergone ESD for EGC reversed overexpression of cIAP2 and suppressed cell apoptosis.

Keywords: Cellular inhibitor of apoptosis protein 2; Gastric carcinogenesis; Helicobacter pylori.

MeSH terms

  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Apoptosis / genetics*
  • Baculoviral IAP Repeat-Containing 3 Protein
  • Carcinogenesis / genetics*
  • Carcinoma / complications
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Carcinoma / surgery
  • Clarithromycin / therapeutic use
  • Down-Regulation
  • Endoscopic Mucosal Resection
  • Gastritis, Atrophic / complications
  • Gastritis, Atrophic / genetics*
  • Gastritis, Atrophic / metabolism
  • Gastritis, Atrophic / pathology
  • Helicobacter Infections / complications
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / genetics*
  • Helicobacter Infections / metabolism
  • Helicobacter pylori
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Metaplasia
  • Neoplasm Staging
  • Omeprazole / therapeutic use
  • Proton Pump Inhibitors / therapeutic use
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Stomach / pathology
  • Stomach Neoplasms / complications
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Anti-Bacterial Agents
  • Inhibitor of Apoptosis Proteins
  • Proton Pump Inhibitors
  • RNA, Messenger
  • Amoxicillin
  • BIRC3 protein, human
  • Baculoviral IAP Repeat-Containing 3 Protein
  • Ubiquitin-Protein Ligases
  • Clarithromycin
  • Omeprazole