Brief Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 14, 2011; 17(42): 4718-4724
Published online Nov 14, 2011. doi: 10.3748/wjg.v17.i42.4718
CpG island methylator phenotype in plasma is associated with hepatocellular carcinoma prognosis
Ji-Bin Liu, Yi-Xin Zhang, Shu-Hui Zhou, Min-Xin Shi, Jin Cai, Yan Liu, Ke-Ping Chen, Fu-Lin Qiang
Ji-Bin Liu, Yi-Xin Zhang, Ke-Ping Chen, Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China
Ji-Bin Liu, Min-Xin Shi, Jin Cai, Yan Liu, Fu-Lin Qiang, Institute of Tumor, Nantong Tumor Hospital, Nantong 226361, Jiangsu Province, China
Shu-Hui Zhou, Department of Radiology, School of Radiology and Public Health, Soochow University, Suzhou 215006, Jiangsu Province, China
Author contributions: Liu JB and Chen KP designed the study and analyzed and interpreted data; Zhang YX and Cai J revised critically for important intellectual content; Zhou SH did statistical analysis of data; Shi MX and Qiang FL were responsible for acquisition of data.
Supported by The Department of Health of Jiangsu Province, China, No. H200957
Correspondence to: Ke-Ping Chen, Professor, Institute of Life Sciences, Jiangsu University, 301 Xuefu Rd., Zhenjiang 212013, Jiangsu Province, China.
Telephone: +86-511-88791923 Fax: +86-511-88791923
Received: May 17, 2011
Revised: July 14, 2011
Accepted: July 21, 2011
Published online: November 14, 2011

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, DLC-1, SFRP-1, DKK and E-cad.

RESULTS: The frequencies of high-level methylation in HCC tissue and plasma were at least 15% for the seven genes: APC, 48/108, 44.44% in tissue and 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; DLC-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 tissue 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.

Keywords: CpG island methylator phenotype, Methylation, Plasma, Prognosis, Hepatocellular carcinoma