Both authors contributed equally to this work.
Hypomethylation of long interspersed nuclear element-1 promoter is associated with poor outcomes for curative resected hepatocellular carcinoma
Article first published online: 5 AUG 2013
© 2013 The Authors. Liver International published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Volume 34, Issue 1, pages 136–146, January 2014
How to Cite
Liver Int. 2014: 34:136–146
- Issue published online: 10 DEC 2013
- Article first published online: 5 AUG 2013
- Accepted manuscript online: 27 JUN 2013 02:15AM EST
- Manuscript Accepted: 20 JUN 2013
- Manuscript Received: 4 FEB 2013
- Key Scientific and Technological Research Foundation. Grant Numbers: 2008ZX10002-018, No. BWS11J074
- the Capital Medical Research and Development Fund
- Hepatocellular carcinoma;
- long interspersed nuclear element-1;
Epigenetic alterations are well documented in hepatocarcinogenesis. However, hypomethylation of long interspersed nuclear element 1(LINE-1) promoter and its relationship with clinicopathological features in hepatocellular carcinoma (HCC) remain unknown.
The bisulfite-specific PCR and DNA sequencing analysis was performed to assess the methylation status of LINE-1 promoter in a pilot cohort of 71 patients with HCC. Additionally, methylation levels of two hot CpG sites of LINE-1 promoter, site 7 and 18 were measured by real-time PCR and compared with clinicopathological parameters in a cohort of 172 HCC. All the patients included were in BCLC stage A or B.
Most patients with HCC (87.3%) showed hypomethylation of LINE-1 promoter compared with HBV-related cirrhosis and normal controls (P < 0.001). The HCC patients with LINE-1 promoter hypomethylation had a median tumour-free survival (TFS) and overall survival (OS) post-resection of 22.0 (95% CI: 13.3–30.7) months and 35.0 (95% CI: 24.0–46.1) months, respectively, compared with 40 months and ~60 months for those with LINE-1 promoter hypermethylation (P < 0.05). Multivariate analyses showed that the hypomethylation level at CpG site 7 and 18 of LINE-1 promoter, along with tumour size and tumour differentiation, was independently associated with both TFS and OS for patients with HCC after resection.
Promoter hypomethylation of LINE-1, especially at the CpG site 7 and 18, was associated with a poor prognosis in HCC.