title: Cell-free methylation markers with diagnostic and prognostic potential in hepatocellular carcinoma.
abstract: 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.
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.affiliation: Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Shih-Ya
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Peng
authors.affiliation: Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Pu-Yeh
authors.initials: PY
authors.lastname: Kan
authors.affiliation: Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Wan-Chi
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Yen
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D000074166:Circulating MicroRNA / Q000097:blood / Q000235:genetics*; D000074141:Circulating Tumor DNA / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D056945:Hep G2 Cells; D006505:Hepatitis / Q000097:blood / Q000821:virology; D006509:Hepatitis B / Q000097:blood / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D015203:Reproducibility of Results; D012307:Risk Factors; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: C097353:AFP protein, human; D014408:Biomarkers, Tumor; D000074166:Circulating MicroRNA; D000074141:Circulating Tumor DNA; D000509:alpha-Fetoproteins
keywords: DNA methylation; diagnosis; hepatocellular carcinoma; marker; microRNA