Frequent DNA methylation of MiR-129-2 and its potential clinical implication in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis and high mortality due to a lack of effective medical treatment and apparent early stage symptoms. Understanding molecular mechanism of cancer development is crucial for HCC diagnosis, prognosis, and treatment. Recently,...

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Published in:Genes chromosomes & cancer 2013-07, Vol.52 (7), p.636-643
Main Authors: Lu, Chang-Yi, Lin, Kai-Yuan, Tien, Meng-Tsung, Wu, Cheng-Tao, Uen, Yih-Huei, Tseng, Tzu-Ling
Format: Article
Language:English
Subjects:
Aged
Carcinoma, Hepatocellular - blood
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Diagnosis, Differential
DNA Methylation - genetics
Early Detection of Cancer
Female
Fibrosis - blood
Fibrosis - genetics
Fibrosis - metabolism
Gene Expression Regulation, Neoplastic
Gene Silencing
Hep G2 Cells
Humans
Liver Neoplasms - blood
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Male
MicroRNAs - genetics
MicroRNAs - isolation & purification
Middle Aged
Prognosis
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Summary:Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis and high mortality due to a lack of effective medical treatment and apparent early stage symptoms. Understanding molecular mechanism of cancer development is crucial for HCC diagnosis, prognosis, and treatment. Recently, microRNAs have been shown to play an important role in carcinogenesis, being regulated by DNA methylation in several cases. In this study, a whole genome approach was used to identify methylation‐regulated miRNAs in HCC, finally focusing on miR‐129‐2. MiR‐129‐2 methylation and reduced expression were observed in all examined HCC cell lines but not in normal liver cells and tissues. In 39 (93%) of 42 HCC, the methylation levels of miR‐129‐2 were significantly increased in tumor tissues compared with adjacent normal tissues. Furthermore, miR‐129‐2 methylation was detectable in plasma samples from HCC patients, but not in plasma samples from healthy individuals or patients with liver cirrhosis. At a cut‐off value of −2.36 (log2 transformation of methylation level), it was possible to distinguish HCC from healthy and cirrhotic controls with sensitivity and specificity of 88% and 100%, respectively. This study indicates that miR‐129‐2 methylation is highly accurate in distinguishing HCC patients from cirrhosis patients and healthy individuals, implying its potential utility as an early diagnostic marker for HCC. © 2013 Wiley Periodicals, Inc.
ISSN:1045-2257
1098-2264
DOI:10.1002/gcc.22059