Relationship between Helicobacter pylori Tyrosine-Phosphorylated CagA-Related Markers and the Development of Diffuse-Type Gastric Cancers: A Case-Control Study

Abstract

Background/Aims: Tyrosine phosphorylation of the EPIYA motif in Helicobacter pylori CagA (CagA-P) plays an important role in toxic reaction. Diffuse-type gastric cancer (DGC) has a poor prognosis. We tried to clarify the expression level of CagA-P in DGC patients. Methods: We enrolled 42 early-stage DGC patients (DGC group; 20 males, 22 females, mean age 58.2 years) and 42 age- and gender-matched atrophic gastritis (AG) patients (AG group) as controls. We evaluated histological and serological gastritis and examined two markers; the serum titer of anti-CagA-P antibody and CagA-P expression in gastric mucosa. Results: In the DGC group, we found significantly higher corpus histological gastritis scores for activity, atrophy, and intestinal metaplasia. The titer of anti-CagA-P antibody and CagA-P expression in the corpus were significantly higher in the DGC group, especially in females (p < 0.05). Sixteen patients (38.1%) in the DGC group showed both positive markers, and the odds ratio for DGC occurrence was 4.00 (95% CI = 1.07–14.91), while that for females was 9.00 (95% CI = 1.29–62.97). Conclusions: CagA-P plays a role in active corpus gastritis, which may link to DGC carcinogenesis. Clinical quantification of CagA-P-related markers may be useful for the evaluation of DGC risk, especially in females.

Serum screening for detection of high‐risk group for early‐stage diffuse type gastric cancer in Japanese

“…10 Another of our previous studies also demonstrated that the correlation between the grade of gastritis and gastric carcinogenesis was clearer in women than in men. Generally, malignant tumors as well as IGC are male dominant.…”

“…Interestingly, we have reported the implication of phosphorylated CagA in DGC carcinogenesis and its effect was distinct in women. 10 Another of our previous studies also demonstrated that the correlation between the grade of gastritis and gastric carcinogenesis was clearer in women than in men. 24 The reason is not clear; however, a difference in immunological systems after adhesion of H. pylori may exist.…”

“…In our previous work, we found that the presence of active gastritis in the corpus may be characteristic in DGC patients, and that active inflammation in the gastric corpus may be linked to high phosphorylated CagA expression derived from H. pylori on the surface epithelium. 10 Until now, nodular gastritis has been reported as an important predictive status for DGC development. 14,15 Endoscopic findings detected nodular appearance in the gastric antrum; however, corpus active gastritis was accompanied by nodular appearance in these patients, and this may be an important indicator of DGC development.…”

Serum Helicobacter Pylori CagA Antibody As A Biomarker For Gastric Cancer in East-Asian Countries

“…In the latest article, Wada et al examined the expression level of tyrosine phosphorylation of the EPIYA motif in CagA (CagA-P) in diffuse-type gastric cancer patients [51]. The serum titer of anti-CagA-P antibody was significantly higher in the gastric cancer group than in the matched atrophic gastritis group, especially in females.…”

Biomarkers for Helicobacter Pylori Infection and Gastroduodenal Diseases

“…At present, there are no reports that examined the prevalence of east Asian type CagA-specific antibodies in sera although there is a sandwich ELISA system to detect east Asian type CagA strains [43]. In addition, Wada et al examined the level of tyrosine phosphorylation of the EPIYA motif in CagA (CagA-P) in patients with diffuse-type gastric cancer in Japan [44]. The serum titer of anti-CagA-P antibodies was significantly higher in the gastric cancer group than in the matched control group.…”