Significance of methylation status of MASPIN gene and its protein expression in prognosis of gallbladder cancer.

Abstract

We investigated prognostic significance of methylation status of MASPIN gene and its protein expression in normal subjects, cholelithiasis and gallbladder cancer (GBC) patients. MASPIN protein expression and its promoter methylation in gallbladder tissue of cholelithiasis (n=36), GBC (n=46) and controls (n=25) were investigated. Clinicopathological parameters and prognosis of patients with GBC were correlated with protein expression of MASPIN. Survival analysis of GBC patients was performed using Kaplan-Meier method. Significant increased (P<0.0001) protein expression of MASPIN was observed in GBC as compared to cholelithiasis, whereas negligible expression was found in normal tissues. Methylation-specific PCR revealed statistical significant (P=0.005) difference in methylation status of MASPIN promoter between gallstone and GBC patients. Significant association was observed between methylation profile with protein expression of MASPIN (P=0.004), stage (P=0.011) and cellular differentiation (P=0.012) for GBC. Also, significant (P=0.004) difference in survival was observed for malignant patients having demethylated MASPIN promoter. Further significant negative correlation (Pearson's coefficient [r]=-0.617; P<0.0001) was observed between MASPIN expression and survival of cancer patients after surgery. Overall survival was significantly shorter (P≤0.0001; hazard ratio [HR] for death=2.84; 95% confidence interval [CI],0.09865-0.3683) in patients of GBC with MASPIN expression ≥169.56pg/mg (median survival; 10months) with compared to those with expression <169.56pg/mg (median survival; 16months). Overexpression of MASPIN protein may play an important role in malignant progression and is correlated with a poor prognosis. Also MASPIN DNA methylation can be used as a novel therapeutic target for treating GBC.