Methylation Status Of MUC2 Gene In Pancreatic Carcinoma And Its Diagnostic Value In Early Stage Of Pancreatic Carcinoma

Effective new markers of pancreatic carcinoma are urgently needed. In this study, we evaluate the potential contribution of MUC2 methylation to pancreatic adenocarcinoma and to establish a feasible method to detect the promoter methylation of MUC2 gene in pancreatic cancer. MUC2 mRNA expression was evaluated using RT-PCR, whereas MUC2 protein expression was evaluated by immunohistochemistry. Detection of aberrant MUC2 gene promoter methylation in pancreatic cancer cell lines by MSP. Methylation -sensitive restriction Endonuclease(MS-RE)-PCR method was used to detect the promoter methylation of MUC2 gene in peripheral blood and feces of pancreatic cancer patients. Both MUC2 mRNA expression and MUC2 protein expression was restored in ASPC,CFPAC-1 and SW1990 pancreatic cancer cell lines when after the methyltransferse inhibitor treatment. The methylation site was observed in ASPC,CFPAC-1 and SW1990 cells using MSP. The methylation positive rate of MUC2 was 40.0%(16/40) in peripheral blood specimens of pancreatic cancer patients and 36.7%(11/30) in feces of pancreatic cancer patients. No methylated MUC2 sequences were detected in 15 peripheral blood specimens of Chronic pancreatitis patients and 8 feces specimens of Chronic pancreatitis patients. Of the 25 cases of peripheral blood specimens and 20 cases of feces specimens of normal controls, the MUC2 gene was shown to be methylated in 1 cases, respectively(4.0%,5.0%). MUC2 methylation both in peripheral blood and feces specimens were 40%(4/10) in pancreatic cancer, whereas no MUC2 methylation were detected in chronic pancreatitis and normal control. Aberrant methylation of MUC2 is highly correlated with inhibition of MUC2 gene transcription. Peripheral blood and feces specimens could be easily and safety obtained. Detecting aberrant methylation of MUC2 from peripheral blood and feces specimens may be a new tool to diagnose pancreatic cancer.