Int J Biol Sci 2012; 8(4):451-458. doi:10.7150/ijbs.4038

Research Paper

The Silencing of RECK Gene is Associated with Promoter Hypermethylation and Poor Survival in Hepatocellular Carcinoma

Changsong Zhang1,2,4*, Yang Ling1*, Chenghui Zhang3*, Yun Xu3, Lu Gao2, Rong Li2, Jing Zhu1, Lieying Fan4, Lixin Wei2 ✉

1. Clinical Oncology Laboratory, Changzhou Tumor Hospital, Soochow University, Changzhou, China;
2. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China;
3. Department of Oncology, Nanyang Center Hospital, Nanyang, China;
4. Department of Clinical Laboratory, Shanghai East Hospital, Tongji University Medical School, Shanghai, China.
* These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Zhang C, Ling Y, Zhang C, Xu Y, Gao L, Li R, Zhu J, Fan L, Wei L. The Silencing of RECK Gene is Associated with Promoter Hypermethylation and Poor Survival in Hepatocellular Carcinoma. Int J Biol Sci 2012; 8(4):451-458. doi:10.7150/ijbs.4038. Available from

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Background: To evaluate the promoter methylation status of RECK gene and mRNA expression in patients with hepatocellular carcinoma (HCC).

Methods: We analyzed RECK methylation by MSP, and RECK mRNA by real-time PCR in 74 HCC. The liver cell lines (7721, Chang and Hep-G2) were treated with 5-Aza-CdR and TSA.

Results: RECK mRNA were lower in HCC tissues (Mean -∆Ct = -3.29) than that in Non-Hcc tissues (Mean -∆Ct = -2.42). Expression of RECK was elevated in only 24 (32.43%) of the 74 HCC patients but decreased (-∆∆Ct<0) in 50 (67.57%) of the patients. RECK promoter was hypermethylated in 55.4% (41/74) of HCCs, and in only 17.6% (13/74) of Non-Hcc samples. RECK mRNA were lower in HCC patients with hypermethylation (∆MI>=0.5) (Mean -∆∆Ct = -1.75) than those with demethylation (∆MI<0.5) (Mean -∆∆Ct = 0.05), and there is a decreased tendency for RECK mRNA in HCC patients with promoter hypermethylation (p = 0.002). There was a significantly correlation found between RECK mRNA and poor survival after surgery. After treated by 5-Aza-CdR and TSA, we found that RECK mRNA induced different changes in 7721, Chang and Hep-G2 cells. And RECK demethylation also induced by epigenetic inhibitors.

Conclusion: The results suggested that the hypermethylation may lead to promoter silencing of RECK mRNA and associated with poor survival in HCC.

Keywords: RECK, hepatocellular carcinoma, methylation.