Promoter methylation and mRNA expression of DKK-3 and WIf-1 in hepatocellular carcinoma
Promoter methylation and mRNA expression of DKK-3 and WIf-1 in hepatocellular carcinoma
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DOI：
10.3748/wjg.15.2595
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发表时间：
2009-06-07
影响因子：
4.3
通讯作者：
Xiong, Qi-Ru
中科院分区：
文献类型：
--
作者：
Ding, Zhen;Qian, Ye-Ben;Xiong, Qi-Ru
目的：探讨肝细胞癌(HCC)中DKK-3和WIF-1基因的启动子甲基化状态和mRNA表达。方法：DKK-3和WIF-1作为Wnt拮抗剂和抑癌基因，但基因启动子的高甲基化和低mRNA表达异常激活Wnt信号通路，诱导HCC的发生。使用甲基化特异性聚合酶链式反应 (PCR) 研究了 33 名 HCC 患者的肿瘤和邻近非癌组织以及 20 份作为对照的正常肝组织中 DKK-3 和 WIF-1 基因启动子的甲基化状态。还通过实时定量逆转录酶PCR测定DKK-3和WIF-1 mRNA的表达。分析甲基化、mRNA表达量与临床资料的关系，以及两个基因的甲基化和mRNA表达量。结果：HCC中DKK-3和WIF-1基因的甲基化程度较癌旁非癌组织和正常对照组织显着升高（chi(2)=7.79，P < 0.05；chi(2)=4.89，P < 0.05），而与癌旁组织相比，差异无统计学意义。 观察到邻近非癌组织和正常对照组织之间的甲基化。在HCC组织中，DKK-3启动子甲基化在年龄和肝硬化中存在显着差异，WIF-1启动子甲基化在HBsAg和肝硬化中存在显着差异。与正常对照组织相比，HCC及癌旁非癌组织中DKK-3 mRNA的平均表达量显着升高。 WIF-1 mRNA的平均表达量在三种组织中没有显着差异。 HCC中DKK-3基因的mRNA表达量随着病理分级的增加而降低。结论：DKK-3和WIF-1启动子异常甲基化以及DKK-3和WIF-1表达降低可能是HCC发生的重要机制，对HCC的早期诊断和治疗可能具有深远的意义。 (C) 2009 WJG 出版社和百事登。版权所有。
AIM: To investigate the promoter methylation status and mRNA expression of DKK-3 and WIF-1 gene in hepatocellular carcinoma (HCC).METHODS: DKK-3 and WIF-1 acted as Wnt-antagonists and tumor suppressors, but hypermethylation of the gene promoter and low mRNA expression activated Wnt signaling aberrantly and induced the development of HCC. Methylation status of the DKK-3 and WIF-1 gene promoter was investigated using methylation specific polymerase chain reaction (PCR) in tumor and adjacent non-cancerous tissues from 33 HCC patients and 20 normal liver tissues served as control. The expression of DKK-3 and WIF-1 mRNA was also determined by real-time quantitative reverse transcriptase PCR. The relationship between methylation, mRNA expression, and clinical data, as well as methylation and mRNA expression of the two genes were analyzed.RESULTS: The methylation of DKK-3 and WIF-1 genes in HCC increased significantly compared with adjacent non-cancerous tissues and normal control tissues (chi(2) = 7.79, P < 0.05; chi(2) = 4.89, P < 0.05), and no significant difference in methylation between adjacent non-cancerous tissues and normal control tissues was observed. In HCC tissues, significant differences in the DKK-3 promoter methylation were observed in age and cirrhosis, and significant differences of the WIF-1 promoter methylation were observed in HBsAg and cirrhosis. The average expression of DKK-3 mRNA in HCC and adjacent non-cancerous tissues was increased significantly compared with normal control tissues. The average expression of WIF-1 mRNA showed no significant difference among the three tissues. The mRNA expression of DKK-3 gene in HCC was decreased as the pathological grade increased.CONCLUSION: The aberrant promoter methylation and decreased expression of DKK-3 and WIF-1 may be an important mechanism in HCC, and may be a far-reaching significance in early diagnosis and therapy of HCC. (C) 2009 The WJG Press and Baishideng. All rights reserved.