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Promoter hypermethylation of death-associated protein kinase gene in cholangiocarcinoma |
Xiao-Fang Liu, Fan-Min Kong, Zheng Xu, Shao-Ping Yu, Fu-Bo Sun, Cui-Sheng Zhang, Qing-Xian Huang, Xian-Ting Zhou and Zhan-Wen Song |
Yantai, China
Author Affiliations: Department of Hepatobiliary Surgery, Affiliated Yantai Yuhuangding Hospital, Medical College of Qingdao University, Yantai 264000, China (Liu XF, Xu Z, Yu SP, Sun FB, Zhang CS, Huang QX, Zhou XT and Song ZW); and Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, China (Kong FM)
Corresponding Author: Xiao-Fang Liu, MD, Department of Hepato-biliary Surgery, Yantai Yuhuangding Hospital, Medical College of Qingdao University, Yantai 264000, China (Tel: 86-535-6691999; Fax: 86-535-6240341; Email: Liu634@263.net). |
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Abstract BACKGROUND: Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-regulated Ser/Thr kinase which is involved in apoptosis. The aberrant methylation of its promoter region CpG islands may be one of the important mechanisms of carcinogenesis. We studied the relationship of methylation status and expression of the DAPK gene with the clinical findings in cholangiocarcinoma.
METHODS: Target DNA was modified by sodium bisulfite, coverting all unmethylated, but not methylated, cytosines to uracil, and subsequently detected by methylation-specific PCR. Moreover, mRNA expression of the DAPK gene was assessed by RT-PCR.
RESULTS: Aberrant methylation of the DAPK gene was detected in 11 (30.6%) of 36 tissue specimens of cholangiocarcinoma, and in 2 (5.6%) of 36 specimens of adjacent normal tissues. DAPK mRNA was not expressed in tumor and adjacent tissues with hypermethylation of the DAPK promoter. There were no statistical differences in the extent of differentiation and invasion, lymph node metastasis or pathologic type between the methylated and unmethylated tissues.
CONCLUSIONS: The frequency of DAPK gene methylation in cholangiocarcinoma is high and it may offer an effective means for earlier auxiliary diagnosis of the malignancy. The DAPK gene is probably suppressed by methylation, and it could become resistant to apoptosis and immunological surveillance. The DAPK gene epigenetically affected by methylation may be associated with the carcinogenesis of cholangiocarcinoma.
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