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01-12-2008 | Laboratory and Translational Research

Predictive Value of Expression and Promoter Hypermethylation of XAF1 in Hepatitis B Virus-Associated Hepatocellular Carcinoma Treated with Transplantation

Authors: Feng Zhang, PhD, Li-Ming Wu, MD, Lin Zhou, PhD, Qi-Xing Chen, PhD, Hai-Yang Xie, MD, Xiao-Wen Feng, MD, Shu-Sen Zheng, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 12/2008

Abstract

Background

Transcriptional regulation of the putative tumor suppressor gene X-linked inhibitor of apoptosis protein-associated factor 1 (XAF1) by promoter methylation has been related to tumor progression in gastric and bladder cancer. The aim of this study was to investigate the methylation status and expression level of XAF1 in human hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) treated with liver transplantation (LT), and to evaluate potential predictive value for tumor recurrence.

Methods

The expression level and methylation status of XAF1 in three liver cancer cell lines (SMMC-7721, HepG2, and Hep3B) and 65 cases of HBV-associated HCC following LT were analyzed by RT-PCR (RT, reverse-transcriptase), immunohistochemistry, and methylation-specific polymerase chain reaction (PCR).

Results

XAF1 transcripts were not observed or present at low levels in liver cancer cell lines and were restored by treatment with demethylating agent 5-aza-2′-deoxycytidine (5-Aza-dC). In vivo, methylation status was associated with protein level of XAF1 (P < 0.001) and serum level of alpha-fetoprotein (AFP) (P = 0.009). The expression pattern of XAF1 was associated with portal vein tumor thrombi (PVTT), preoperative AFP level, tumor size, and recurrence. Multivariate analysis revealed that expression level of XAF1 was an independent factor for predicting recurrence-free survival [hazard ratio 0.237, 95% confidence interval (CI) 0.095–0.592, P = 0.002]. However, no significant association was found between methylation status and the risk of tumor recurrence.

Conclusion

Promoter hypermethylation is a critical, but not the sole, mechanism for gene silencing of XAF1 in HCC. Protein level of XAF1 may serve as a potential biomarker for tumor recurrence after LT.

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Title: Predictive Value of Expression and Promoter Hypermethylation of XAF1 in Hepatitis B Virus-Associated Hepatocellular Carcinoma Treated with Transplantation
Authors: Feng Zhang, PhD
Li-Ming Wu, MD
Lin Zhou, PhD
Qi-Xing Chen, PhD
Hai-Yang Xie, MD
Xiao-Wen Feng, MD
Shu-Sen Zheng, MD, PhD, FACS
Publication date: 01-12-2008
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 12/2008
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-008-0146-1

Keynote webinar | Spotlight on medication adherence

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Predictive Value of Expression and Promoter Hypermethylation of XAF1 in Hepatitis B Virus-Associated Hepatocellular Carcinoma Treated with Transplantation

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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