Research Papers:

Cell-free methylation markers with diagnostic and prognostic potential in hepatocellular carcinoma

Chang-Yi Lu, Shih-Ya Chen, Hui-Ling Peng, Pu-Yeh Kan, Wan-Chi Chang and Chia-Jui Yen _

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Oncotarget. 2017; 8:6406-6418. https://doi.org/10.18632/oncotarget.14115

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Chang-Yi Lu1, Shih-Ya Chen1, Hui-Ling Peng1, Pu-Yeh Kan1, Wan-Chi Chang1, Chia-Jui Yen2

1Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan

2Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Correspondence to:

Chia-Jui Yen, email: [email protected]

Keywords: hepatocellular carcinoma, DNA methylation, marker, microRNA, diagnosis

Received: July 05, 2016     Accepted: December 16, 2016     Published: December 23, 2016


Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis and high mortality. There is a dearth of effective early diagnostic tools, so liver resection surgery and liver transplantation are the only effective medical treatments. The most commonly used marker for HCC detection is serum alpha fetoprotein (AFP), which has low sensitivity and specificity. Because aberrant DNA methylation of genes and miRNAs occurs early in most cancers, we explored whether circulating methylation markers could be promising clinical tools for HCC diagnosis. Using a whole-genome approach, we identified many hyper-methylated miRNAs in HCC. Furthermore, three abnormally methylated genes and one miRNA were combined to establish a methylation predictive model and tested for its diagnostic and prognostic potential in HCC. Using plasma samples, the predictive model exhibited high sensitivity and specificity (> 80%) for HBV-related HCC. Most importantly, nearly 75% of patients who could not be diagnosed with AFP at 20 ng/mL were detected by this model. Further, the predictive model exhibited an exceedingly high ability to predict 5-year overall survival in HCC patients. These data demonstrate the high diagnostic and prognostic potential of methylation markers in the plasma of HCC patients.

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