Clinical value of CagA, c‑Met, PI3K and Beclin‑1 expressed in gastric cancer and their association with prognosis

Abstract

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.

Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer

“…We showed that high PI3K expression was associated with larger size, lymphatic metastasis, and advanced tumor stage. Other studies support our findings and demonstrate an association of PI3K expression with pathohistological factors and unfavorable outcomes in various solid tumors [36][37][38][39]. High expression of mTOR in our cohort was also associated with advanced tumor stage but not with any other analyzed parameter.…”

Biomarkers of gastric cancer: Current topics and future perspective

“…The measurement and assessment of HGF activity have been crucial role in understanding the tumor microenvironment that prompt tumor metastasis and drug resistance[ 47 ]. The recent immunostaining experiment has presented that MET expression was significantly associated with lymphatic vessel invasion and poor overall survival (OS), implying that the expression of HGF/c-Met pathway might serve as a prospective predictive factor in patients with GC[ 50 , 51 ]. Interestingly, patients with a lower pretreatment HGF level showed a positive response to the treatment of trastuzumab.…”

HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

“…Independent studies have suggested that CagA, the H. pylori effector protein, stimulates cancer-associated signal transduction by forming a complex with MET [182][183][184]. Although there was no significant genotype-phenotype interaction between soluble MET protein and single nucleotide polymorphism (SNPs) of the CagA-related genes, after adding the genetic counts of these SNPs, the diagnostic value of MET protein to distinguish gastric cancer patients from normal individuals improved significantly [176].…”