title: Combination of serum RASSF1A methylation and AFP is a promising non-invasive biomarker for HCC patient with chronic HBV infection.
abstract: BACKGROUND
  Hypermethylation of the promoter region of the RAS association domain family 1A gene (RASSF1A) occurs widely in hepatocellular carcinoma (HCC) tissues. While the diagnostic performance of the use of RASSF1A methylation as a serum or plasma marker in patients with HCC has varied largely in the literature,we confirmed the clinical application value of serum RASSF1A methylation for HBV related HCC in this study.
  
  
  METHODS
  A total of 584 participants were recruited into this study, including 190 patients with HCC, 114 patients with liver cirrhosis (LC), 120 patients with chronic hepatitis B (CHB) and 160 healthy individuals. Serum RASSF1A methylation was determined by the MethyLight method. In addition, we followed up 43 HCC patients who were unable to undergo surgery for 24 months.
  
  
  RESULTS
  Serum RASSF1A methylation occurred significantly more frequently in patients with HCC (122/190, 64.2%) than in patients with LC (20/114, 17.5%), patients with CHB (6/120, 5.0%) and in healthy individuals (0/160, 0) (P < 0.001); moreover, it allowed for the discrimination of patients with HCC from those with CHB with an areas under the ROC curves (AUC) of 0.796 (64.2% sensitivity and 89.8% specificity). Furthermore, the AUC for the combination of serum RASSF1A methylation and AFP level (≥20 ng/L) was 0.876 (80.9% sensitivity and 93.4% specificity). Serum RASSF1A methylation positive in patients with HCC was associated with more malignant clinical characteristics and a worse overall survival (OS) (P < 0.05).
  
  
  CONCLUSIONS
  Serum RASSF1A methylation demonstrated a satisfactory value for in the diagnosis of HBV related HCC, and could predict clinical progression and prognosis. In addition, our findings suggested that the combination of serum RASSF1A methylation and AFP level may be a promising non-invasive biomarker for the discrimination of patients with HCC from those with CHB.
  The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_DPAT-D-15-00090.1.
authors.affiliation: Department of Laboratory Medicine, Hangzhou First People's Hospital, 310006, Hangzhou, China. biodxy82@gmail.com.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Dong
authors.affiliation: The Second Clinical Medical College, Zhejiang Chinese Medical University, 310053, Hangzhou, China. hehui577@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Laboratory Medicine, Hangzhou First People's Hospital, 310006, Hangzhou, China. Zhangweiying369@163.com.
authors.forename: Weiying
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Hangzhou First People's Hospital, 310006, Hangzhou, China. Yudaojun98@163.com.
authors.forename: Daojun
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Laboratory Medicine, Hangzhou First People's Hospital, 310006, Hangzhou, China. wangxj0525@hotmail.com.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Hangzhou First People's Hospital, 310006, Hangzhou, China. hzsylab@163.com.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000401:mortality / Q000821:virology; D019175:DNA Methylation; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood* / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000097:blood*; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D000509:alpha-Fetoproteins