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

Aim: We investigated prognostic significance of methylation status of MASPIN gene and its protein expression in normal subjects, cholelithiasis and gallbladder cancer (GBC) patients.

Methods: 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.

Results: 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 ≥169.56 pg/mg (median survival; 10 months) with compared to those with expression <169.56 pg/mg (median survival; 16 months).

Conclusion: 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.