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Promoter methylation of cysteine dioxygenase type 1: gene silencing and tumorigenesis in hepatocellular carcinoma
Ann Hepatobiliary Pancreat Surg 2017 Nov;21(4):181-7
Published online November 30, 2017
Copyright © 2017 Ann Hepatobiliary Pancreat Surg.

Jung-il Choi1, Eung-Ho Cho1, Sang Bum Kim1, Ryounggo Kim2, Junhye Kwon3, Misun Park3, Hye-Jin Shin3, Han Suk Ryu4, Sun-Hoo Park5, and Kee-Ho Lee6

1Department of Surgery, Korea Cancer Center Hospital, Seoul, 2Department of Surgery, Dongnam Institution of Radiological & Medical Sciences, Busan, 3Department of Translational Research, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, 4Department of Pathology, Seoul National University Hospital, Seoul, 5Department of Pathology, Korea Cancer Center Hospital, Seoul, 6Division of Radiation Cancer Research, Korea Institute of Radiological and Medication Sciences, Seoul, Korea
Received August 7, 2017; Accepted August 11, 2017.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Backgrounds/Aims: Cysteine dioxygenase type 1 (CDO1) acts as a tumor suppressor and is silenced by promoter methylation in various malignancies. The relationship between the CDO1 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 CDO1 down-regulation. The SNU423 cells transfected with the CDO1 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: CDO1 was activated after demethylation treatment in the HCC specimens. Moreover, tumor cell proliferation, colony-forming, migration, and invasion activities significantly decreased after CDO1 transfection (p<0.05). The percentage of tumors that were larger than 5 cm was higher in patients who had a lower expression of CDO1 (p=0.030). Vascular invasion and histological grade were independent prognostic factors for poor overall and recurrence-free survival. The degree of CDO1 expression was not an independent prognostic factor in this study’s population. Conclusions: These results suggested that methylation down-regulated CDO1 expression in the HCC cells. CDO1 methylation may be a potentially valuable diagnostic biomarker for HCC. (Ann Hepatobiliary Pancreat Surg 2017;21:181-187)
Keywords : Hepatocellular carcinoma; Cysteine dioxygenase type 1; DNA methylation; Demethylation; Biomarker

 

November 2018, 22 (4)