Expressions And Significance Of Death-associated Protein Kinase 1 In Esophageal Squamous Cell Carcinoma

BACKGROUNDEsophageal squamous cell carcinoma(ESCC) is the commonly malignant tumor, which the incidence is 10-15/100 000.ESCC often arises from preceding dysplastic lesions in the oesophageal epithelium,with the result of the inactivation of antioncogene,the activation of oncogene and the instability of genomic,and so on. However,the molecular changes occurring in premalignant lesions are not well understood.Death-associated protein kinase 1(DAP-Kinase) is a novel serine/threonine kinase which induce cell to apoptosis by many signal paths.A previous study suggested that dapk contribute to the disequilibrium of cell proliferation and apoptosis,leading to development of the tumor after the accumulation of the mutative gene and arresting the cell cycle in the G1 phase.The inactivation of DAPK1 gene was found in wide variety of human cancers and cell line.The methylation of CpG island is one of the main mechanisms for gene.Inactivation.OBJECTIONOur study is to examined the DAPK1 CpG island for hypermethylation and the expression of the DAPK1 protein in the ESCC tissue,and compared the results with the development of the ESCC.METHODS56 patients with ESCC and 30 patients with a background of non-neoplastic epithelium,adjacent to the ESCC were studied.The promoter methylation status of DAPK1 was examined by methylation-specific polymerase chain reaction(MSP),and the expression of the DAPK1 protein was analyzed by immunohistochemistry.The clinical data including sex,age,tumor stage and node metastasis was collected.RESULTS1.The expression rate of protein in esophageal squamous cancer was significantly lower than that in the adjacent tissue(36.2%vs63.3%;P=0.015＜0.05),while there was no significant difference between the poorly differentiated and the adjacented epithelium(X~2=8.605,P=0.003＜0.05);2.The state of methylation in cancer was significantly higher than that in the adjacent tissue(60.3%vs33.3%;P=0.016＜0.05),while there was no significant difference between the poorly differentiated and the adjacented epithelium(X~2=5.557, P=0.018＜0.05);3.81.1%(30/37) promoter mehtylation in tissue with the negative expression of protein,while there was unmethylation in highly positive expression.We found that promoter methylation of DAPK1 was significantly associated with negative immunostaining of DAPK1(X~2=18.362,P=0.000,r=-0.563) while comparing the.DNA methylation and the expression of protein;4.There was no significant difference while comparing the expression of DAPK1 with clinical data including sex,age,tumor stage and node metastasis.CONCLUSIONS1.There was no association between the expression of DAPK1 and clinical data including sex,age,tumor stage and node metastasis;2.The expression of DAPK1 protein is low in ESCC,and which is negatively correlation with the difference of tumor.The abberant of expression may contribute to the development of ESCC; 3.The methylation state of DAPK1 is high in ESCC,and which is positive correlation with the difference of tumor while the expression of protein was positive. The methylation state decrease the expression of the protein,leading to the development of ESCC.