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Predictive value of expression and promoter hypermethylation of XAF1 in hepatitis B virus-associated hepatocellular carcinoma treated with transplantation.
- Source :
-
Annals of surgical oncology [Ann Surg Oncol] 2008 Dec; Vol. 15 (12), pp. 3494-502. Date of Electronic Publication: 2008 Oct 02. - Publication Year :
- 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.<br />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).<br />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.<br />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.
- Subjects :
- Adaptor Proteins, Signal Transducing
Adult
Aged
Apoptosis Regulatory Proteins
Azacitidine pharmacology
Carcinoma, Hepatocellular complications
Carcinoma, Hepatocellular surgery
Female
Gene Expression Regulation, Neoplastic
Hepatitis B complications
Hepatitis B virology
Hepatitis B virus genetics
Humans
Immunoenzyme Techniques
Intracellular Signaling Peptides and Proteins
Liver Neoplasms complications
Liver Neoplasms surgery
Male
Middle Aged
Neoplasm Proteins metabolism
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local surgery
Prognosis
RNA, Messenger genetics
RNA, Messenger metabolism
RNA, Neoplasm genetics
RNA, Neoplasm metabolism
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Survival Rate
Tumor Cells, Cultured
Zinc Fingers
Carcinoma, Hepatocellular genetics
DNA Methylation
Hepatitis B genetics
Liver Neoplasms genetics
Liver Transplantation
Neoplasm Proteins genetics
Promoter Regions, Genetic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1534-4681
- Volume :
- 15
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Annals of surgical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 18830757
- Full Text :
- https://doi.org/10.1245/s10434-008-0146-1