Promoter methylation of cysteine dioxygenase type 1: gene silencing and tumorigenesis in hepatocellular carcinoma.

BACKGROUNDS/AIMS: Cysteine dioxygenase type 1 () acts as a tumor suppressor and is silenced by promoter methylation in various malignancies. The relationship between the methylation status and hepatocellular carcinoma (HCC) tumorigenesis was evaluated.

METHODS

Using a HCC cell line (SNU423), an in vitro demethylation study was performed to confirm whether promoter methylation causes down-regulation. The SNU423 cells transfected with the cell function was compared to that of naïve cells. An in vivo study using immunohistochemical staining of HCC specimens that were collected from patients who underwent curative liver resection was also performed.

RESULTS

was activated after demethylation treatment in the HCC specimens. Moreover, tumor cell proliferation, colony-forming, migration, and invasion activities significantly decreased after transfection (<0.05). The percentage of tumors that were larger than 5 cm was higher in patients who had a lower expression of (=0.030). Vascular invasion and histological grade were independent prognostic factors for poor overall and recurrence-free survival. The degree of expression was not an independent prognostic factor in this study's population.

CONCLUSIONS

These results suggested that methylation down-regulated expression in the HCC cells. methylation may be a potentially valuable diagnostic biomarker for HCC.