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

• Published in: Annals of surgical oncology 2008-12, Vol.15 (12), p.3494-3502
• Main Authors: Zhang, Feng, Wu, Li-Ming, Zhou, Lin, Chen, Qi-Xing, Xie, Hai-Yang, Feng, Xiao-Wen, Zheng, Shu-Sen
• Format: Article
• Language: English
• Subjects: Adult; Aged; Azacitidine - pharmacology; Carcinoma, Hepatocellular - complications; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - surgery; DNA Methylation; Female; Gene Expression Regulation, Neoplastic; Hepatitis B - complications; Hepatitis B - genetics; Hepatitis B - virology; Hepatitis B virus; Hepatitis B virus - genetics; Humans; Immunoenzyme Techniques; Intracellular Signaling Peptides and Proteins; Laboratory and Translational Research; Liver Neoplasms - complications; Liver Neoplasms - genetics; Liver Neoplasms - surgery; Liver Transplantation; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - surgery; Oncology; Prognosis; Promoter Regions, Genetic - genetics; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Surgery; Surgical Oncology; Survival Rate; Tumor Cells, Cultured; Zinc Fingers
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-008-0146-1

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