Gastric cancer (GC) is the fourth most common type of malignant tumor worldwide, and causes the second highest number of cancer-associated mortalities in 2012. Gastric tumorigenesis is a multistep and multifactorial process. In the present study, tissue microarray and immunohistochemistry analysis were used to detect cytotoxin-associated gene A (CagA), c-Met, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and Beclin-1 expression in 121 GC tumors and 120 normal gastric tissues. The clinical relevance and prognostic implications of CagA, c-Met, PI3K and Beclin-1 expression in GC patients were analyzed. Furthermore, the Cox proportional hazards model was performed to indicate the independent prognostic factors for GC patients, including various clinicopathological parameters and CagA, c-Met, PI3K and Beclin-1 expression. The results indicated that CagA-positive H. pylori infection, c-Met, PI3K and Beclin-1 may have major roles in the oncogenesis, invasion and lymph node metastasis of GC. The disease-free survival rate was negatively associated with the expression of c-Met and CagA in tissues, and was positively associated with Beclin-1 expression. Overall survival was also negatively associated with the expression of c-Met and PI3K, and was positively associated with Beclin-1 expression. This indicated that c-Met and Beclin-1 may be independent and efficient biomarkers for predicting the DFS of patients with GC. Furthermore, in CagA-positive H. pylori infection-associated GC, c-Met expression was significantly upregulated and Beclin-1 expression was significantly downregulated. CagA-positive H. pylori infection therefore associated with the c-Met signaling pathway and the suppression of autophagy in the neoplasia, invasion and metastasis of GC.
Keywords: Beclin-1; CagA; PI3K; c-Met; gastric cancer; prognosis.