Brief Article
Copyright ©2010 Baishideng. All rights reserved
World J Gastroenterol. Feb 14, 2010; 16(6): 755-763
Published online Feb 14, 2010. doi: 10.3748/wjg.v16.i6.755
Methylation of Dickkopf-3 as a prognostic factor in cirrhosis-related hepatocellular carcinoma
Bin Yang, Zhi Du, Ying-Tang Gao, Cheng Lou, Shi-Guang Zhang, Tong Bai, Yi-Jun Wang, Wen-Qin Song
Bin Yang, Zhi Du, Ying-Tang Gao, Key Laboratory of Artificial Cells, Third Central Hospital, Tianjin 300170, China
Zhi Du, Cheng Lou, Yi-Jun Wang, Department of Hepatobiliary Surgery, Third Central Hospital, Tianjin 300170, China
Tong Bai, Graduate School of Tianjin Medical University, Tianjin 300070, China
Bin Yang, Ying-Tang Gao, Shi-Guang Zhang, Wen-Qin Song, College of Life Science, Nankai University, Tianjin 300071, China
Bin Yang, Postdoctoral Workstation of TEDA, Tianjin 300457, China
Author contributions: Du Z and Song WQ designed the research and revised the manuscript; Yang B, Zhang SG and Bai T performed the research; Gao YT provided the analytic tools; Lou C collected the clinical pathological data; Wang YJ collected the tumor tissues; Yang B analyzed the data and wrote the manuscript.
Supported by China Postdoctoral Science Foundation, No. 20070410753; Tianjin Science and Technology Commission, No. 05YFSZSF02500; and Tianjin Health Bureau, No. 07KZ10
Correspondence to: Zhi Du, Professor, Key Laboratory of Artificial Cells, Third Central Hospital, Tianjin 300170, China. zhi-du@163.com
Telephone: +86-22-84112148 Fax: +86-22-24315132
Received: October 20, 2009
Revised: November 26, 2009
Accepted: December 3, 2009
Published online: February 14, 2010
Abstract

AIM: To investigate the prevalence and time of Dickkopf (DKK) family methylation and its clinical significance in hepatocarcinogenesis.

METHODS: Methylation of DKK family genes was quantitatively analyzed in 115 liver tissue samples, including 50 pairs of primary hepatocellular carcinoma (HCC) and matched noncancerous cirrhotic tissue samples, as well as 15 liver cirrhosis biopsy samples.

RESULTS: The methylation level of DKK3 was significantly higher in HCC tissue samples than in matched noncancerous cirrhotic tissue samples (P < 0.0001) or in liver cirrhosis biopsy samples (P = 0.0139). Receiver operator characteristic curve analysis confirmed that the percent of methylated reference (PMR) values of DKK3 could effectively discriminate HCC tissue samples from noncancerous tissue samples (AUC = 0.8146) or liver cirrhosis biopsy samples (AUC = 0.7093). Kaplan-Meier survival curves revealed that the progression-free survival time of patients with a higher DKK3 methylation level (PMR > 1%) was significantly shorter than that of those with a lower DKK3 methylation level (PMR ≤ 1%) (P = 0.0255). Multivariate Cox analysis indicated that methylated DKK3 was significantly and independently related with a shorter survival time (relative risk = 2.527, 95% CI: 1.063-6.008, P = 0.036) of HCC patients.

CONCLUSION: Methylation of DKK3 is an important event in early malignant transformation and HCC progression, and therefore might be a prognostic indicator for risk assessment of HCC.

Keywords: Dickkopf; Hepatocellular carcinoma; Methylation; Biomarker; Prognosis