ABSTRACT
Objective:To investigate the relationship between Helicobacter pylori(HP) cytotoxin-associated gene A (HP-CagA), HP isolate vacuole-forming toxin gene A (HP-VacA) and gastric cancer occurrence and clinical pathological factors.Methods:Eighty-eight patients with gastric cancer from January 2018 to January 2020 in Suzhou Hospital Affiliated of Anhui Medical University was selected as the observation group, 80 patients with benign gastric lesions during the same period was selected as the benign control group, and 80 healthy patients was selected as the healthy control group. The clinical data, HP-CagA, HP-VacA positive expression rates of the three groups were compared, the risk factors of gastric cancer were analyzed, and the relationship between HP-CagA, HP-VacA and gastric cancer clinicopathological factors were evaluated.Results:Family history of gastric cancer, high-salt diet, preference for hot food, decreased pepsinogen (PG)Ⅰ/PGⅡ, combined with fatty liver, increased triglyceride, total cholesterol and low density lipoprotein cholesterin, smoking and depression were risk factors of gastric cancer ( P<0.05). The positive rate of HP-CagA, HP-VacA in the observation group were higher than those in the benign control group and the healthy control group: 82.93%(73/88) vs. 62.50%(50/80) and 26.25%(21/80), 30.68%(27/88) vs. 7.50%(6/80) and 0, the differences were statistically significant ( P<0.05). The positive of HP-CagA and HP-VacA had correlation with age, pathological type, and degree of differentiation of gastric cancer ( P<0.05). The 1-year survival rate of HP-CagA and HP-VacA positive patients was lower than that of negative patients by Kaplan-Meier analysis ( P<0.05). Conclusions:The positive of HP-CagA and HP-VacA in HP infections are closely related togastric cancer. Strengthening the treatment of HP infection patients with positive HP-CagA and HP-VacA has important clinical value and social significance for cutting off the early stage of gastric cancer and improving prognosis.
ABSTRACT
Objective: To explore the effect of Helicobacter pylori virulence factor cytotoxin-associated gene A protein (CagA) on the extracellular regulated protein kinase (ERK) signaling pathway, and to elucidate the carcinogenesis mechanism of CagA. Methods: The pcDNA3. 1/CagA eukaryotic expression vector was constructed, and the gastric cancer AGS cells were divided into blank control group (blank vector transfection), CagA transfection group (GZ7/CagA transfection), and CagA + ERKi group (ERK1/2 inhibitor pretreatment + GZ7/CagA transfection). The expression levels of CagA, phosphorylated ERK (p-ERK), total ERK (T-ERK), B-lymphocytoma-2 (Bcl-2), Bcl-2-related X protein (Bax) and cleaved caspase-3 proteins in the cells in various groups were determined by Western blotting method. The activities of AGS cells in various groups were determined by CCK-8 method, and the apoptotic rates of AGS cells were determined by flow cytometry. Results: Compared with blank control group, the expression levels of CagA, p-ERK, and Bel-2 proteins in CagA transfection group were significantly increased (P<0. 01), and the expression levels of Bax and cleaved caspase-3 proteins were significantly decreased (P<0. 01). Compared with CagA transfection group, the expression levels of p-ERK and Bel-2 proteins in CagA+ERKi group were significantly decreased (P<0. 01), and the expression levels of Bax and cleaved caspase-3 proteins were significantly increased (P<0. 01). Compared with CagA transfection group, the activities of gastric cancer cells in CagA + ERKi group at different time points were significantly decreased (P< 0. 01). Compared with CagA transfection group, the apoptotic rate of gastric cancer cells in CagA + ERKi group was significantly increased (P<0. 05). Conclusion: Helicobacter pylori virulence factor CagA can inhibit the proliferation of gastric cancer cells and promote the apoptosis of gastric cancer cells, and its mechanism may be related to the activation of ERK signaling pathway by CagA.