Prognostic value of Wnt inhibitory factor-1 expression in hepatocellular carcinoma that is independent of gene methylation
Prognostic value of Wnt inhibitory factor-1 expression in hepatocellular carcinoma that is independent of gene methylation
复制标题
肝细胞癌中 Wnt 抑制因子-1 表达与基因甲基化无关的预后价值
DOI：
10.1007/s13277-010-0117-6
复制
发表时间：
2011-02-01
期刊：
影响因子：
--
通讯作者：
Yuan, Yun-Fei
中科院分区：
文献类型：
--
作者：
Huang, Liang;Li, Mei-Xiang;Yuan, Yun-Fei
近年来，研究发现Wnt抑制因子-1（WIF-1）在多种实体瘤中表观遗传学失活，但WIF-1甲基化和表达状态在肝细胞癌（HCC）中的生物学和临床意义尚不清楚。本研究应用逆转录聚合酶链反应（PCR）和甲基化特异性PCR检测了肝癌细胞系中WIF-1的表达和甲基化。此外，105例HCC中WIF-1的甲基化和表达状态与临床病理参数和肿瘤切除后的预后相关。WIF-1在一个肝癌细胞系和L02中表达，这两个细胞系的启动子区均未甲基化。在其他4个不表达WIF-1的肝癌细胞系中检测到WIF-1启动子的DNA高甲基化。在肿瘤和非肿瘤组织样本中，WIF-1甲基化率分别为61.9%和37.1%（P = 0.001）。与邻近非肿瘤组织相比，肿瘤组织中WIF-1在信使核糖核酸（mRNA）水平上显著下调（P = 0.006）。WIF-1甲基化与WIF-1表达呈负相关（P = 0.017，R = -0.232）。WIF-1的甲基化与患者生存率无关。相反，WIF-1 mRNA表达阴性的患者的总生存率较低。这些结果表明，WIF-1的异常甲基化是肝癌发生过程中的常见事件。此外，WIF-1的表达，而不是甲基化，是接受HCC切除术的患者的良好预后的预测因子。
Recently, Wnt inhibitory factor-1 (WIF-1) was found to be epigenetically inactivated in several solid tumors, but the biological and clinical relevance of WIF-1 methylation and expression status in hepatocellular carcinoma (HCC) are still unclear. In the present study, reverse transcription polymerase chain reaction (PCR) and methylation-specific PCR were used to examine the WIF-1 expression and methylation in HCC cell lines. In addition, methylation and expression status of WIF-1 in 105 HCC cases were correlated with clinicopathological parameters and prognosis after tumor resection. WIF-1 was expressed in one HCC cell line and L02, both of which were not methylated in promoter region. DNA hypermethylation of WIF-1 promoter was identified in the other four HCC cell lines without WIF-1 expression. In neoplastic and non-neoplastic tissue samples, the rates of WIF-1 methylation were 61.9% and 37.1% (P = 0.001), respectively. WIF-1 was significantly downregulated in neoplastic tissues at messenger ribonucleic acid (mRNA) level, as compared to adjacent non-neoplastic tissues (P = 0.006). A significant inverse association was observed between WIF-1 methylation of and WIF-1 expression (P = 0.017, R = -0.232). Methylation of WIF-1 was not associated with patient survival. In contrast, patients whose tumors exhibited negative WIF-1 mRNA expression had lower rates of overall survival. These findings suggested that aberrant methylation of WIF-1 is a common event in hepatocarcinogenesis. In addition, expression, but not methylation, of WIF-1 is a predictor of good outcome in patients undergoing resection of HCC.