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DNA methyltransferase expression and DNA methylation in human hepatocellular carcinoma and their clinicopathological correlation.

Authors
 Bong-Kyeong Oh  ;  Haeryoung Kim  ;  Young Nyun Park  ;  Chanil Park  ;  Jinsub Choi  ;  Yhong-Hee Shim  ;  Hye-Jung Park 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, Vol.20(1) : 65-73, 2007 
Journal Title
 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 
ISSN
 1107-3756 
Issue Date
2007
MeSH
Carcinoma, Hepatocellular/genetics* ; Carcinoma, Hepatocellular/metabolism ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA (Cytosine-5-)-Methyltransferases/metabolism ; DNA Methylation* ; Gene Expression Regulation, Neoplastic* ; Genes, Tumor Suppressor ; Humans ; Liver/metabolism ; Liver Neoplasms/genetics* ; Liver Neoplasms/metabolism ; RNA, Messenger/analysis ; Reverse Transcriptase Polymerase Chain Reaction
Keywords
DNA methylation ; DNA methyltransferase ; hepatocellular carcinoma
Abstract
Aberrant DNA methylation on CpG islands is one of the most consistent epigenetic changes in human cancers, and the methylation process is catalyzed by DNA methyltransferase (DNMT). We evaluated i) the mRNA levels of three DNMTs; DNMT1, DNMT3a and DNMT3b, in 25 hepatocellular carcinomas (HCCs), in their corresponding non-cancerous liver tissues and in 7 normal livers by using real-time reverse transcriptase-polymerase chain reaction; ii) nuclear expression of DNMT1 and DNMT3a proteins in the HCCs by immunohistochemistry, iii) the methylation status of 5 genes; p16, p15, E-cadherin, HIC-1 and RASSF1A in the same tissues, and iv) the relationships between the above results and the clinicopathological characteristics, including prognosis. The differences in mRNA expression levels for DNMT1, DNMT3a and DNMT3b were statistically significant between HCC and normal livers (p<0.001), HCC and chronic hepatitis (p<0.001) and HCC and cirrhosis (p<0.001). An increase in mRNA expression levels of >4-fold for DNMT3b in HCCs was significantly associated with a poorer overall survival (p=0.027) and shorter metastasis-free survival (p=0.0299). A poorer recurrence-free survival was noted in HCCs with a >4-fold increase in DNMT3a mRNA (p=0.0120). The average numbers of methylated genes were 0, 1.27, 1.38 and 2.72 for normal livers, chronic hepatitis, cirrhosis and HCCs, respectively, and this progressive increase from normal livers to chronic hepatitis/cirrhosis through HCC may suggest that tumor suppressor gene methylation is an early event in hepatocarcinogenesis. These results first suggest that hepatocarcinogenesis involves an increased expression of DNMT1, DNMT3a and DNMT3b mRNA and a progressive increase in the number of methylated genes from normal liver, chronic hepatitis/cirrhosis to HCC and secondly that an increase in the DNMT3a and DNMT3b mRNA levels in HCCs relative to their non-cancerous tissues may be a predictor of poor survival.
Full Text
http://www.spandidos-publications.com/ijmm/20/1/65
DOI
10.3892/ijmm.20.1.65
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
Yonsei Authors
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Oh, Bong Kyeong(오봉경)
Choi, Jin Sub(최진섭)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96177
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