Department of Surgical Pathology, Changhua Christian Hospital, Taiwan.
Swiss Med Wkly. 2010 Jul 15;140:w13065. doi: 10.4414/smw.2010.13065. eCollection 2010.
It has been postulated that the induced suppressor of cytokine signalling (SOCS) protein inhibits the signalling pathway through the association with a variety of tyrosine kinase proteins, and decelerates or inhibits the progression of cirrhosis and hepatocellular carcinoma (HCC). The purpose of this study was to investigate the expression of SOCS1 gene in HCC and explore the potential molecular mechanisms.
We investigated CpG island methylation status at the promoter region and the expression of the SOCS1 gene in 46 HCC tumour and paired non-tumour samples.
This immuno-histochemical study demonstrated strong homogeneous or heterogeneous staining in the non-tumour liver tissue compared to a marked decreased heterogeneous staining in the HCC (p 0.001). Real-time quantitative (qRT)-PCR showed that SOCS1 mRNA was also down-regulated in tumour cells of HCC. The methylation analysis of CpG sites at the promoter region of SOCS1 disclosed hypermethylation in 39% of HCC samples and 41% of non-tumour tissue. Promoter methylation of SOCS1 was well correlated with HCC derived from liver cirrhosis (p = 0.044) and tumour size (p = 0.038).
Our findings suggest a tumour suppressor-like role of SOCS1 in the hepatocarcinogenesis of human HCC.
据推测，细胞因子信号转导的诱导抑制剂（SOCS）蛋白通过与多种酪氨酸激酶蛋白结合，抑制信号通路，从而减缓或抑制肝硬化和肝细胞癌（HCC）的进展。本研究旨在研究 HCC 中 SOCS1 基因的表达，并探讨其潜在的分子机制。
我们研究了 46 例 HCC 肿瘤和配对非肿瘤样本中启动子区域的 CpG 岛甲基化状态和 SOCS1 基因的表达。
这项免疫组织化学研究表明，非肿瘤肝组织的染色均匀或不均匀，而 HCC 的染色明显不均匀（p<0.001）。实时定量（qRT）-PCR 显示 SOCS1 mRNA 在 HCC 的肿瘤细胞中也下调。SOCS1 启动子区 CpG 位点的甲基化分析显示，39%的 HCC 样本和 41%的非肿瘤组织存在高甲基化。SOCS1 的启动子甲基化与由肝硬化引起的 HCC（p=0.044）和肿瘤大小（p=0.038）密切相关。
我们的研究结果表明，SOCS1 在人类 HCC 的发生中起肿瘤抑制因子样作用。
