Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 7, 2012; 18(17): 2043-2052
Published online May 7, 2012. doi: 10.3748/wjg.v18.i17.2043
Aberrant methylation of SPARC in human hepatocellular carcinoma and its clinical implication
Ye Zhang, Bin Yang, Zhi Du, Tong Bai, Ying-Tang Gao, Yi-Jun Wang, Cheng Lou, Feng-Mei Wang, Yu Bai
Ye Zhang, Zhi Du, Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China
Ye Zhang, Zhi Du, Tong Bai, Yi-Jun Wang, Cheng Lou, Feng-Mei Wang, Yu Bai, The Third Central Hospital of Tianjin, Tianjin 300170, China
Bin Yang, Ying-Tang Gao, Tianjin Key Laboratory of Artificial Cell, Tianjin 300170, China
Author contributions: Zhang Y performed the experiments and wrote the manuscript; Yang B, Bai T and Gao YT provided vital reagents and were involved in editing the manuscript; Wang YJ, Lou C, Wang FM and Bai Y collected all the human materials; Du Z designed the study and revised the manuscript.
Supported by Tianjin Health Bureau for research projects, No. 09KY04, No. 2010KZ17 and No. 11KG112
Correspondence to: Zhi Du, Professor of Medicine, The Third Central Hospital of Tianjin, Tianjin 300170, China. zhi-du@163.com
Telephone: +86-22-84112148 Fax: +86-22-24315132
Received: September 30, 2011
Revised: November 25, 2011
Accepted: February 27, 2012
Published online: May 7, 2012
Abstract

AIM: To investigate the methylation status of secreted protein acidic and rich in cysteine (SPARC) in human hepatocellular carcinoma (HCC) and evaluate its clinical implication.

METHODS: The methylation status of SPARC was analyzed in one HCC cell line (SMMC-7721) and 60 pairs of HCC and corresponding nontumorous tissues by methylation-specific polymerase chain reaction and bisulfite sequencing. The expression of SPARC mRNA and protein were examined by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. The correlations between the methylation status and the gene expression, the clinicopathological parameters, as well as the prognosis after surgery were analyzed.

RESULTS: In the SMMC-7721 cell line, the loss of SPARC expression was correlated with the aberrant methylation and could be reactivated by the demethylating agent 5-aza-2’-deoxycytidine. Methylation frequency of SPARC in HCC was significantly higher than that in the corresponding nontumorous tissues (45/60 vs 7/60, P < 0.001), and it was correlated with the pathological classification (P = 0.019). The downregulation of the SPARC mRNA expression in HCC was correlated with the SPARC methylation (P = 0.040). The patients with methylated SPARC had a poorer overall survival than those without methylated SPARC (28.0 mo vs 41.0 mo, P = 0.043).

CONCLUSION: Aberrant methylation is an important mechanism for SPARC inactivation in HCC and SPARC methylation may be a promising biomarker for the diagnosis and prognosis of HCC.

Keywords: Biomarker; Diagnosis; Hepatocellular carcinoma; Methylation; Prognosis; Tumor suppressor gene