Abstract

The MUC4 gene could have a key role in theprogression of pancreatic cancer, but the quantitative measurement of itsexpression in clinical tissue samples remains a challenge. The correlationsbetween MUC4 promoter methylation status in vivo and either pancreatic cancerprogression or MUC4 mRNA expression need to be demonstrated. We used thetechniques of quantitative real-time PCR and DNA methylation-specific PCRcombined microdissection to precisely detect MUC4 expression and promotermethylation status in 116 microdissected foci from 57 patients with pancreaticductal adenocarcinoma. Both mRNA expression and hypomethylation frequencyincreased from normal to precancerous lesions to pancreatic cancer.Multivariate Cox regression analysis showed that high-level MUC4 expression (P= 0.008) and tumor-node-metastasis staging (P = 0.038) were significantindependent risk factors for predicting the prognosis of 57 patients. The MUC4mRNA expression was not significantly correlated with promoter methylationstatus in 30 foci of pancreatic ductal adenocarcinoma. These results suggestthat high mRNA expression and hypomethylation of the MUC4 gene could beinvolved in carcinogenesis and in the malignant development of pancreaticductal adenocarcinoma. The MUC4 mRNA expression may become a new prognosticmarker for pancreatic cancer. Microdissection-based quantitative real-time PCRand methylation-specific PCR contribute to the quantitative detection of MUC4expression in clinical samples and reflect the epigenetic regulatory mechanismsof MUC4 in vivo.