摘要
AIM： To evaluate the clinical significance of CpG island methylator phenotype （CIMP） in plasma and its association with hepatocellular carcinoma （HCC） progress. METHODS： CIMP status of 108 HCC patients was analyzed using a methylation marker panel in tumor tissues and plasma with methylation-specific polymerase chain reaction. Fifteen samples of non-neoplastic liver tissues and 60 of plasma from healthy persons were examined simultaneously. Examined genes included APC, WIF-1, RUNX-3, DI C-1, SFRP-1, DKK and E-cad.26/108, 24.07% in plasma; WIF-1, 53/108, 49.07% in tissue and 35/108, 32.41% in plasma; RUNX-3, 52/108, 48.14% in tissue and 42/108, 38.89% in plasma; DIC-1, 38/108, 35.18% in tissue and 23/108, 21.30% in plasma; SFRP-1, 40/108, 37.04% in tissue and 31/108, 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 tissues or plasma of healthy persons. CIMP status in tumor tissues differed significantly in gender, hepatitis B surface antigen, alpha-fetoprotein, and tumor-node- metastasis stage （P 〈 0.05）. Similar results were obtained with plasma samples （P 〈 0.05）. There was no difference in CIMP status in age, presence of hepatitis C virus antibody, cirrhosis, number of nodes, number of tumors, tumor size, or Edmondson-Steiner stage. A one-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 sample source for CIMP analysis. CIMP in plasma may serve as a molecular marker of late-stage and poor-prognosis HCC.
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.
基金
Supported by The Department of Health of Jiangsu Province,China,No.H200957
