Quantitative methylation analysis reveals distinct association between PAX6 methylation and clinical characteristics with different viral infections in hepatocellular carcinoma.
BACKGROUND
Related to genetic alteration, frequent promoter hypermethylation is also a contributing factor in the development of human cancers. Recently, we discovered numerous novel genes that were aberrantly methylated in hepatocellular carcinoma (HCC) by using Infinium HumanMethylation27 BeadChip array. We utilized a quantitative methylation-specific PCR (Q-MSP) system for the evaluation of PAX6 methylation in 29 normal controls and 160 paired HCC tissues and their adjacent non-tumor tissues. We verified the correlation between the methylation status of PAX6 and clinical characteristics with different viral status.


RESULTS
Paired-box 6 promoter methylation was observed in 39.4 %, 15.6 %, and 3.4 % in primary HCCs, adjacent non-tumors, and normal control tissues, respectively. Methylation of the PAX6 promoter region in HCCs significantly increased compared with control tissues. PAX6 was frequently methylated in HCV-positive HCC tissues (61.3 %) and rarely methylated in HBV-positive (22.1 %) and double-negative HCC tissues (33.3 %).


CONCLUSIONS
Our data suggests that promoter hypermethylation of PAX6 is a common event in HCCs and the association of PAX6 methylation in clinicopathological features is divergent with different viral status.
Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Yu-Lueng
YL
Shih
Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Chih-Chi
CC
Kuo
Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Republic of China.
Ming-De
MD
Yan
Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China ; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Ya-Wen
YW
Lin
Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Chung-Bao
CB
Hsieh
Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Tsai-Yuan
TY
Hsieh
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000821:virology*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D000071841:PAX6 Transcription Factor / Q000235:genetics*; D011401:Promoter Regions, Genetic
D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human
DNA methylation; HCV; Hepatocellular carcinoma; PAX6; Q-MSP