Clinicopathological And Prognostic Implications Of Snail And MGAT5in Patients With Gastric Cancer

Part I:Clinicopathological and prognostic implications of Snail in patients with gastric cancerPurpose:The present study was to investigate the clinical significance of Snail, a zinc-finger transcription factor, in the development and progression of gastric cancer.Methods:Protein and mRNA levels of Snail and its target gene E-cadherin expression, as well as cancer stem cell phenotype in four human gastric cancer cells with various differentiation statuses were examined using Western blot, reverse transcription-PCR, quantitative real-time PCR, and flow cytometry respectively. Immunohistochemistry staining and evaluation of Snail expression in human normal gastric samples versus clinicopathologically characterized stomach cancer tissues followed by statistical analyses were applied to evaluate prognostic value of Snail expression for progression and patient survival of gastric carcinomas.Results:Functional Snail expression interlinks dedifferentiation status with cancer stem cell phenotype in gastric cancer cells. Upregulation of Snail expression during clinical gastric cancer progression was significantly associated with clinicopathological parameters including the tumor cell differentiation, local tumor growth, lymph node status, distant metastasis, and tumor stage. Increased Snail expression in gastric cancer tissues was positively correlated with poor overall survival of gastric cancer patients. Further multivariate Cox regression analyses suggested that Snail expression was an independent prognostic indicator for the disease.Conclusions:Our data suggest that Snail expression could be a reliable independent prognostic factor to predict stomach carcinoma progression, which might open a new avenue for potential clinical intervention with functional Snail expression in gastric cancer patients. Part Ⅱ:Clinicopathological and prognostic implications of β1,6N-acetylglucosaminyltransferase V (MGAT5) in patients with gastric cancerPurpose:The present study was to investigate the clinicopathological and prognostic values of MGAT5and improve the risk stratification in patients with gastric cancer.Methods:MGAT5expression was retrospectively analyzed by immunohistochemistry in three independent sets comprising313patients with gastric adenocarcinoma. Results were assessed for association with clinical features and overall survival by using Kaplan-Meier analysis. Prognostic values of MGAT5expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating MGAT5expression was determined in patients with late-stage gastric cancer by using receiver operating characteristic (ROC) analysis.Results:Low intratumoral MGAT5density, which was associated with poor differentiation, N classification, TNM stage, and Kiel stage, was an independent prognosticator for poor overall survival. Combination of intratumoral MGAT5expression and TNM or Kiel staging systems had a better predictive power for overall survival. Applying the prognostic value of intratumoral MGAT5density to TNM stage and Kiel stage groups showed a better prognostic value in patients with gastric cancer.Conclusion:Integrating intratumoral MGAT5density that was recognized as an independent prognostic marker into current clinical staging systems significantly improved prognostic stratification of patients with gastric cancer. This refined risk stratification scheme might aid in appropriate therapeutic options and ultimately improve the outcomes of patients with advanced-stage disease.