title: Frequent DNA methylation of MiR-129-2 and its potential clinical implication in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Lu
authors.forename: Kai-Yuan
authors.initials: KY
authors.lastname: Lin
authors.forename: Meng-Tsung
authors.initials: MT
authors.lastname: Tien
authors.forename: Cheng-Tao
authors.initials: CT
authors.lastname: Wu
authors.forename: Yih-Huei
authors.initials: YH
authors.lastname: Uen
authors.forename: Tzu-Ling
authors.initials: TL
authors.lastname: Tseng
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D003937:Diagnosis, Differential; D055088:Early Detection of Cancer; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000302:isolation & purification; D008875:Middle Aged; D011379:Prognosis
chemical_list: D035683:MicroRNAs; C541915:Mirn129 microRNA, human