Gastric Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Aug 28, 2008; 14(32): 5000-5007
Published online Aug 28, 2008. doi: 10.3748/wjg.14.5000
Mechanism and pathobiologic implications of CHFR promoter methylation in gastric carcinoma
Yu-Jia Gao, Yan Xin, Jian-Jun Zhang, Jin Zhou
Yan Xin, Yu-jia Gao, The Fourth Laboratory of Cancer Institute & Department of Tumor Pathology of General Surgery Institute, The First Affiliated Hospital of China Medical University, Shengyang 110001, Liaoning Province, China
Jian-Jun Zhang, Jin Zhou, Department of Surgery and Internal Medicine, Liaoning Tumor Hospital, Shengyang 110042, Liaoning Province, China
Author contributions: Gao YJ, Xin Y contributed equally to this work; Gao YJ and Xin Y designed and performed the research; Gao YJ and Xin Y were responsible for data management and analysis; Zhang JJ and Zhou J assisted with the data collection and provided specimens; Gao YJ wrote the manuscript.
Supported by The National Natural Science Foundation of China, No. 30371607, the Special Scientific Research Foundation for Distinguished Researchers, Education Department of Liaoning Province, No. 2006R53
Correspondence to: Yan Xin, The Fourth Laboratory of Cancer Institute & Department of Tumor Pathology of General Surgery Institute, The First Affiliated Hospital of China Medical University, Shengyang 110001, Liaoning Province, China. yxin@mail.cmu.edu.cn
Telephone: +86-24-83282351 Fax: +86-24-83282351
Received: June 4, 2008
Revised: August 11, 2008
Accepted: August 18, 2008
Published online: August 28, 2008
Abstract

AIM: To investigate the aberrant methylation of CHFR promoter in human gastric cancer (GC) and its impact on the expression of CHFR mRNA and protein, as well as its correlation with clinical and histological features of human GC.

METHODS: Methylation-specific polymerase chain reaction (MSPCR) was used to detect the methylation status of CHFR promoter in 20 primary GC samples and paired normal gastric mucosa. The CHFR mRNA and protein expressions were investigated both by RT-PCR and by Western blotting. The CHFR protein expression in 69 GC samples was immunohistochemically examined.

RESULTS: The DNA methylation of the CHFR gene was found in 9 of the 20 GC samples (45%) and the down-regulation of CHFR mRNA and protein was significantly associated with the methylation status of the CHFR gene (P = 0.006). In 20 samples of corresponding non-neoplastic mucosa, no DNA methylation of the CHFR gene was detected. The CHFR gene methylation in poorly differentiated GC samples was significantly higher than that in well-differentiated GC samples (P = 0.014). Moreover, the negative CHFR protein expression rate in paraffin-embedded GC samples was 55.07% (38/69), the positive rate in poorly differentiated GC samples was 36.73% (18/49), which was significantly lower than 65.00% (13/20) in well-differentiated GC samples (χ2 = 4.586, P = 0.032).

CONCLUSION: Aberrant methylation of the CHFR gene may be involved in the carcinogenesis and development of GC, and is the predominant cause of down-regulation or loss of CHFR mRNA or protein expression. As aberrant methylation of CHFR promoter is correlated with tumor differentiation, it may help to predict the prognosis of GC and CHFR may become a novel target of gene therapy for GC in the future.

Keywords: CHFR gene, Gastric carcinoma, DNA methylation