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Methylation-Mediated Silencing of SOCS-1 Gene in Hepatocellular Carcinoma Derived from Cirrhosis

Second Department of Surgery, Nagoya University School of Medicine, Nagoya, Japan

Purpose: Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of Janus kinase and signal transducer and activation of transcription pathway. Recently, it was demonstrated that SOCS-1 gene was silenced frequently by methylation of CpG island in human hepatocellular carcinoma (HCC). We examined the methylation-mediated silencing of SOCS-1 in tumors of HCC patients.

Experimental Design: Fifty patients with HCC were investigated in this study. We examined the methylation status of the SOCS-1 promoter region by methylation-specific PCR and then confirmed the methylation-mediated silencing of SOCS-1 by Northern blot analysis. Furthermore, this methylation status was compared with clinicopathological findings.

Results: Aberrant methylation of the SOCS-1 gene was detected in 30 of 50 (60%) HCC specimens. No corresponding nontumorous liver tissues showed SOCS-1 methylation. Subsequent Northern analysis proved that methylation of the SOCS-1 promoter inactivated translation and diminished expression of SOCS-1 mRNA. We then analyzed the correlation between the clinicopathological data and SOCS-1 aberrant methylation and found that HCC derived from liver cirrhosis had a significant relationship with SOCS-1 methylation (P = 0.0207).

Conclusions: SOCS-1 may be a novel tumor suppressor, and its aberrant methylation may be a key event for HCC transformation of cirrhotic nodules.