Methylation status of suppressor of cytokine signaling-1 gene in hepatocellular carcinoma
Methylation status of suppressor of cytokine signaling-1 gene in hepatocellular carcinoma
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DOI：
10.1007/s00535-003-1343-0
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发表时间：
2004-06-01
影响因子：
6.3
通讯作者：
Koike, K
中科院分区：
文献类型：
--
作者：
Miyoshi, H;Fujie, H;Koike, K
背景细胞因子信号转导抑制因子（SOCS-1）基因编码区CpG岛的异常甲基化导致SOCS-1沉默在肝细胞癌（HCC）中已有报道。然而，主要是5 '非编码区的甲基化而不是编码区的甲基化决定基因表达的调控。方法.采用甲基化特异性PCR方法检测22例HCC组织和2个细胞系中SOCS-1基因5 '端非编码区和CpG岛的甲基化状态。结果使用CpG岛中的引物，22个HCC样本中有9个表现出SOCS-1的异常甲基化，而22个相邻的非HCC样本中只有1个表现出异常甲基化。在22例HCC中的1例和22例非HCC样本中的5例中检测到非甲基化模式。因此，SOCS-1的异常甲基化与HCC显著相关（Fisher精确检验P = 0.0076）。使用5 '-非编码区的引物，在22个HCC中的12个和2个非HCC样品中观察到异常甲基化。未甲基化模式在5/22例HCC和10/22例非HCC样本中观察到（P = 0.0042）。SOCS-1的甲基化状态与临床病理结果，如肝硬化的存在或不存在或HCC的组织学分级之间没有显著相关性。结论. SOCS-1基因异常甲基化与肝癌的发生有显著相关性。在5 '-非编码区和CpG岛中异常甲基化的比率相似。SOCS-1异常甲基化可能与肝癌发生有关，但仍需进一步研究。
Background. Silencing of the suppressor of cytokine signaling (SOCS-1) by aberrant methylation at the CpG island in the coding region gene has been reported in hepatocellular carcinoma (HCC). However, principally, it is methylation in the 5'-noncoding region but not that in the coding region which determines the regulation of gene expression. Methods. Methylation-specific PCR was performed for the analysis of methylation status both in the 5'-noncoding region and the CpG island of SOCS-1 from 22 HCC tissue samples with adjacent non-HCC tissue samples and from two cell lines. Results. Using primers in the CpG island, 9 of 22 HCC samples exhibited aberrant methylation of SOCS-1, while only 1 of 22 adjacent non-HCC samples did so. The unmethylation pattern was detected in 1 of 22 HCC and in 5 of 22 non-HCC samples. Thus, aberrant methylation of SOCS-1 was significantly associated with HCC (P = 0.0076 by Fisher's exact test). Using primers in the 5'-noncoding region, aberrant methylation was observed in 12 of 22 HCC and in 2 non-HCC samples. The unmethylated pattern was observed in 5 of 22 HCC and in 10 of 22 non-HCC samples (P = 0.0042). There was no significant correlation between the methylation status of SOCS-1 and clinicopathological findings, such as the presence or absence of cirrhosis or the histological grade of HCC. Conclusions. Aberrant methylation of the SOCS-1 had a significant correlation with HCC. The rate of aberrant methylation was similar in the 5'-noncoding region and in the CpG island. Aberrant methylation of SOCS-1 may be associated with hepatocarcinogenesis, although further studies are necessary.