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Gut Liver. 2017;11(1):79-86.

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

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제1저자 윤혁 · 교신저자 김상균

PMID 27282269 PMC5221864 DOI 10.5009/gnl15585 IF 4.1 소화기내과
소속 (5)
  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
  2. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  3. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
  4. Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
  5. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.

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 2Gastric carcinogenesisHelicobacter pylori

Figures

Fig. 1
Fig. 1 Heat map of the Human Apoptosis RT2 ProfilerTM PCR Array. The gene symbol, value of log2 fold change of mRNA expression, and reliability of the data are presented at the bottom. OKAY, A, and B indicate good, moderate, and poor data reliability, respectively. In the top grid, the magnitude of the log2 fold change in mRNA expression of each gene is represented by the color of each square. Red indicates mRNA overexpression, and green indicates reduced mRNA expression. *Among the 5 IAP family genes analyzed (Survive, cIAP1, cIAP2, XIAP, and NAIP), the expression of only cIAP2 (BIRC3) mRNA increased (by 1.85-fold) in subjects with H. pylori-positive early gastric cancer compared with the expression in H. pylori-negative controls without atrophic gastritis or intestinal metaplasia (row C, column 9).
Fig. 2
Fig. 2 Expression of cIAP2 mRNA detected by real-time polymerase chain reaction in five groups classified according to the status of Helicobacter pylori infection, atrophic gastritis/intestinal metaplasia, and gastric cancer. There was a significant difference in the relative expression of cIAP mRNA among the five groups (p<0.001). (a) Normal control, (b) H. pylori (+) and AG/IM (−), (c) H. pylori (−) and AG/IM (+), (d) H. pylori (+) and AG/IM (+), (e) H. pylori-positive EGC. AG, atrophic gastritis; IM, intestinal metaplasia; EGC, early gastric cancer. *Post hoc analysis showed that the expression of cIAP2 was significantly higher in the groups with H. pylori (+), AG/IM (+) (d) and H. pylori-positive EGC (e) than in the controls (a) (p<0.005).
Fig. 3
Fig. 3 The expression of cIAP2 mRNA detected by real-time PCR in patients with Helicobacter pylori-positive early gastric cancer before endoscopic submucosal dissection and at the 12-month follow-up: (A) eradication group; (B) noneradication group. In the eradication group, the expression of cIAP2 mRNA decreased significantly at the 12-month follow-up time point (p=0.006). In the noneradication group, there was no difference in the expression of cIAP2 mRNA before and 12 months after endoscopic submucosal dissection (p=0.14).
Fig. 4
Fig. 4 Representative immunohistochemical staining for cIAP2 protein in patients with Helicobacter pylori-positive early gastric cancer before and 12 months after endoscopic submucosal dissection (ESD) (original magnification, ×200). (A) Strong expression of cIAP2 in the eradication group before ESD; (B) faint expression of cIAP2 in the eradication group at the 12-month follow-up; (C) strong expression of cIAP2 in the non-eradication group before ESD; (D) strong expression of cIAP2 in the noneradication group at the 12-month follow-up. In the eradication group, the expression of cIAP2 protein decreased at 12-month follow-up. In the noneradication group, there was no difference in cIAP2 protein expression before and 12 months after ESD.
Fig. 5
Fig. 5 Representative terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining of gastric tissues from patients with Helicobacter pylori-positive early gastric cancer before endoscopic submucosal dissection (ESD) and at the 12-month follow-up (original magnification, ×200). (A) Eradication group before ESD; (B) eradication group at the 12-month follow-up; (C) noneradication group before ESD; (D) non-eradication group at the 12-month follow-up. In the eradication group, cell apoptosis assayed by using TUNEL increased at the 12-month follow-up. In the noneradication group, there was no difference in cell apoptosis before ESD and at the 12-month follow-up.

그림 출처: PubMed Central 공개 논문 (PMC5221864)

그 밖의 정보
출판 형태
Journal Article
저널
Gut and liver · eISSN 2005-1212
MeSH
Amoxicillin / therapeutic use · Anti-Bacterial Agents / therapeutic use · Apoptosis / genetics · Baculoviral IAP Repeat-Containing 3 Protein · Carcinogenesis / genetics · Carcinoma / complications / genetics / pathology / surgery · Clarithromycin / therapeutic use · Down-Regulation · Endoscopic Mucosal Resection · Gastritis, Atrophic / complications / genetics / metabolism / pathology · Helicobacter Infections / complications / drug therapy / genetics / metabolism · Helicobacter pylori · Humans · Immunohistochemistry · In Situ Nick-End Labeling · Inhibitor of Apoptosis Proteins / genetics / 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 / genetics / pathology / surgery · Ubiquitin-Protein Ligases / genetics / 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
참고문헌
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