Epigenetic alteration of the SOCS1 gene in hepatocellular carcinoma.

PRINCIPLES 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. METHODS 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. RESULTS 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). CONCLUSIONS Our findings suggest a tumour suppressor-like role of SOCS1 in the hepatocarcinogenesis of human HCC.