Abstract
BackgroundHypermethylation 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.MethodsA 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.ResultsSerum 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).ConclusionSerum 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.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_DPAT-D-15-00090.1
Highlights
Hypermethylation of the promoter region of the RAS association domain family 1A gene (RASSF1A) occurs widely in hepatocellular carcinoma (HCC) tissues
The serum levels of alanine aminotransferase (ALT) and total bilirubin (TBIL) were obviously higher in cases of HCC, liver cirrhosis (LC) and chronic hepatitis B (CHB) compared with the healthy controls (P < 0.05), whereas the albumin (ALB) and platelet (PLT) levels were higher in the healthy controls (P < 0.05)
Methylation status of RASSF1A in the serum Methylation of RASSF1A in the serum was detected in 122 of 190 (64.2 %) from patients from the HCC group, in 20 of 114 (17.5 %) patients from the LC group and in 6 of 120 (5.0 %) patients from the CHB group, but no methylation of RASSF1A was detected in the healthy controls
Summary
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. Depending on currently clinical diagnostic tools, the patients with HCC may not undergo the most effective treatment as most of them have already progressed to advanced stages by the time they are diagnosed. There is an urgent need for the identification of effective diagnostic and prognostic biomarkers for HCC
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