RUNX3Methylation, Loss of RUNX3 Expression and Clinicopathologic Findings according toHelicobacter pyloriCagA in Gastric Carcinoma

Abstract

Background/Aims: Helicobacter pylori cytotoxin-associated gene A (CagA) has been suggested to be involved in the inactivation of Runt-related transcription factor 3 (RUNX3), a known gastric carcinoma tumor suppressor gene. It remains unclear how H. pylori CagA initiates or maintains RUNX3 promoter methylation and inactivates its protein expression in gastric carcinoma. Methods: RUNX3 promoter methylation status, RUNX3 expression, and H. pylori CagA were investigated in 76 sample pairs of gastric carcinoma tissue. The patients' medical records were reviewed. The association between RUNX3 methylation or loss of RUNX3 expression and clinicopathologic variables according to H. pylori CagA status were investigated. Results: In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation did not show association with lymphatic invasion, venous invasion, and TNM stages. However RUNX3 methylation was observed more frequently in poorly differentiated adenocarcinoma and signet ring cell carcinoma (77.8% vs. 20.0%, p=0.023) in early stage. In gastric carcinoma patients with H. pylori CagA-positive infection, loss of RUNX3 expression did not show association with lymphatic invasion, venous invasion, and TNM stages. However loss of RUNX3 expression was observed more frequently in early gastric carcinoma than in advanced gastric carcinoma (84.2% vs. 75.0%, p=0.51), but this difference was not significant. Conclusions: In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation or loss of RUNX3 expression did not show correlation with lymphovascular invasion and TNM stages. In early gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation was observed more in poorly differentiated adenocarcinoma and signet ring cell carcinoma. (Korean J Gastroenterol 2015;66:75-84)

Helicobacterpylori inhibits autophagic flux and promotes its intracellular survival and colonization by down‐regulating SIRT1

“…Next, we identified tumour‐suppressive transcriptional factor RUNX3 could regulate expression levels of SIRT1 in gastric cells. It has been revealed that H. pylori infection can inhibit expression of RUNX3 at mRNA levels through CpG island methylation or Src/MEK/ERK and p38 MAPK pathways 41,42 . Work from Tsang et al even showed that H. pylori CagA targets RUNX3 for proteasome‐mediated degradation 43 .…”

“…It has been revealed that H. pylori infection can inhibit expression of RUNX3 at mRNA levels through CpG island methylation or Src/MEK/ERK and p38 MAPK pathways. 41,42 Work from Tsang et al even showed that H. pylori CagA targets RUNX3 for proteasomemediated degradation. 43 The cytoplasmic mislocation of RUNX3 induced by H. pylori infection can also suppress transcriptional activities of RUNX3.…”

Research progress on exosomal proteins as diagnostic markers of gastric cancer (review article)

“…The transmission of CagA into the cytoplasm of the host cell has been shown to play a vital role in H. pylori pathogenesis and GC progression [ 120 , 121 ]. Na et al [ 122 ] reported that patients with poorly differentiated adenocarcinoma and signet ring cell carcinoma of individuals with early GC (EGC) and H. pylori CagA-positive infection exhibited an enhanced methylation of Runt-related transcription factor 3. Simán et al [ 123 ] also drew the conclusion that H. pylori CagA-positive infection is a risk factor of non-cardia gastric adenocarcinoma.…”