AIM:To evaluate the clinical significance of CpG island methylator phenotype(CIMP) in plasma and its asso-ciation with hepatocellular carcinoma(HCC) progress.METHODS:CIMP status of 108 HCC patients wasanalyzed using a methylation marker panel in tumortissues and plasma with methylation-specific poly-merase chain reaction. Fifteen samples of non-neo-plastic liver tissues and 60 of plasma from healthy persons were examined simultaneously. Examinedgenes included APC,WIF-1,RUNX-3,DLC-1,SFRP-1,DKK and E-cad .RESULTS:The frequencies of high-level methylation in HCC tissue and plasma were at least 15% forthe seven genes:APC,48/108,44.44% in tissue and26/108,24.07% in plasma;WIF-1,53/108,49.07% intissue and 35/108,32.41% in plasma;RUNX-3,52/108,48.14% in tissue and 42/108,38.89% in plasma;DLC-1,38/108,35.18% in tissue and 23/108,21.30%in plasma;SFRP-1,40/108,37.04% in tissue and31/108,28.7% in plasma;DKK,39/108,36.1% in tis-sue and 25/108,23.14% in plasma;and E-cad,37/108,34.3% in tissue and 18/108,16.67% in plasma. CIMP+(≥ 3 methylated genes) was detected in 68(60.2%) tumor tissue samples and 62(57.4%) plasma samples.CIMP was not detected in non-neoplastic liver tissuesor plasma of healthy persons. CIMP status in tumortissues differed significantly in gender,hepatitis Bsurface antigen,alpha-fetoprotein,and tumor-node-metastasis stage(P < 0.05) . Similar results were obtained with plasma samples(P < 0.05) . There was nodifference in CIMP status in age,presence of hepatitis C virus antibody,cirrhosis,number of nodes,numberof tumors,tumor size,or Edmondson-Steiner stage. Aone-year follow-up found that the metastatic rate and recurrence rate in the CIMP+ group were significantly higher than in the CIMP- group as assessed with plasma samples(P < 0.05) .CONCLUSION:Plasma DNA can be a reliable samplesource for CIMP analysis. CIMP in plasma may serve asa molecular marker of late-stage and poor-prognosis HCC.
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