The Expression And Methylation Of The Gene XIAP And XAF1in Pancreatic Carcinoma

The pancreatic carcinoma is one of the most common malignant tumors in digestive system, the incidence rate is about2%of all malignant tumors.the fatality rate approaching100%, the overall5-year survival is less than5%.Surgery is the only possible cure for pancreatic cancer, but due to pancreatic anatomy and it’s biological characteristics, and other factors, there are only2.6to9%of patients who can obtain radical resection, but after5years survival rate is only15%-25%. Apoptosis has close relationship with malignant tumor. In order to further study the role of XIAP and XAF1in the pancreatic carcinoma, we study the expression and significance of XIAP and XAF1in pancreatic carcinoma tissues, benign pancreatic disease tissues and normal pancreatic tissues, and study the relationship between status of methylation of XAF1gene promoter and expression of its protein in pancreatic carcinoma.ObjectiveTo study the expression and significance of XIAP and XAF1in pancreatic carcinoma tissues, benign pancreatic disease tissues and normal pancreatic tissues, and study the relationship between status of methylation of XAF1gene promoter and expression of its protein in pancreatic carcinoma. MethodTissue specimens were collected from the department of hepatobiliary surgery of the First Affiliated Hospital of Zhengzhou University from January2008to January2011and classified three groups, which were not received chemotherapy and radiotherapy and proved pancreatic carcinoma except benign pancreatic disease tissues and normal liver tissues by pathology biopsy. Methylation-specific PCR (MSP) and immunohistochemical SP technique were used to detect the status of methylation of XAF1gene promoter and expression of XIAP and XAF1in pancreatic carcinoma (n=48), benign pancreatic disease(n=26) and normal issues(n=15).Results1.The expression rate of XIAP is significantly higher in pancreatic carcinoma (79.2%)than that in benign pancreatic disease tissues(34.6%)and normal pancreatic tissues(27.8%).The expression of XIAP was significantly correlated with histopathological grading (P<0.05).2.the expression rate of XAF1is significantly higher in benign pancreatic disease tissues (84.6%)and normal pancreatic tissues(88.9%)than that in pancreatic carcinoma tissues (52.1%).The expression of XAF1was significantly correlated with lhistopathological grading and clinical stages (P<0.05).3.Negative correlation was observed between the expression of XIAP and XAF1in the pancreatic carcinoma tissues.(r=-0.363,P<0.05).4. In normal issue, there was no promoter methylation of XAF1gene, while in pancreatic carcinoma the rate was31.3%(15/48), and it was related to the tumor TNM stage, pathological grade and lymph node metastasis (P<0.05).The positive rate of XAF1protein expression in pancreatic carcinoma, benign pancreatic disease and normal issues was52.1%(25/48)、84.6%(22/26) and88.9%(16/18).5.There was distinct correlation between methylation of XAF1gene promoter and expression of its protein (x2=13.127P<0.01). Conclusions1.The high expression of XIAP and low expression of XAF1in pancreatic carcinoma, suggesting that the loss of XAF1may resulted the activation of XIAP,then apoptosis was restraint,the cell cycle was unbalanced,that may play an important role in the occurrence and development of pancreatic carcinoma.2.Methylation of promoter might be one of the important factors of inactivation of XAF1gene, and it was related to the clinical stages, pathological grade and lymph node metastasis,it might play an important role in carcinogenesis and progression of pancreatic carcinoma, suggesting that downregulation of XIAP gene or upregulation of XAF1gene in pancreatic carcinoma may become a new target for biological therapy.