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

  • Authors:
    • Bong-Kyeong Oh
    • Haeryoung Kim
    • Hye-Jung Park
    • Yhong-Hee Shim
    • Jinsub Choi
    • Chanil Park
    • Young Nyun Park
  • View Affiliations

  • Published online on: July 1, 2007     https://doi.org/10.3892/ijmm.20.1.65
  • Pages: 65-73
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

Related Articles

Journal Cover

July 2007
Volume 20 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Oh, B., Kim, H., Park, H., Shim, Y., Choi, J., Park, C., & Park, Y.N. (2007). DNA methyltransferase expression and DNA methylation in human hepatocellular carcinoma and their clinicopathological correlation. International Journal of Molecular Medicine, 20, 65-73. https://doi.org/10.3892/ijmm.20.1.65
MLA
Oh, B., Kim, H., Park, H., Shim, Y., Choi, J., Park, C., Park, Y. N."DNA methyltransferase expression and DNA methylation in human hepatocellular carcinoma and their clinicopathological correlation". International Journal of Molecular Medicine 20.1 (2007): 65-73.
Chicago
Oh, B., Kim, H., Park, H., Shim, Y., Choi, J., Park, C., Park, Y. N."DNA methyltransferase expression and DNA methylation in human hepatocellular carcinoma and their clinicopathological correlation". International Journal of Molecular Medicine 20, no. 1 (2007): 65-73. https://doi.org/10.3892/ijmm.20.1.65