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World J Gastroenterol. Apr 21, 2007; 13(15): 2214-2217
Published online Apr 21, 2007. doi: 10.3748/wjg.v13.i15.2214
Hypermethylation and aberrant expression of Wnt antagonist secreted frizzled-related protein 1 in gastric cancer
Cheng-Hai Zhao, Xian-Min Bu, Ning Zhang
Cheng-Hai Zhao, Ning Zhang, Department of Pathophysiology, School of Basic Medicine, China Medical University, Shenyang 110001, Liaoning Province, China
Xian-Min Bu, Department of General Surgery, the Second Affiliated Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
Author contributions: All authors contributed equally to the work.
Supported by Liaoning Education Divison Foundation, No. 05L557
Correspondence to: Dr. Cheng-Hai Zhao, Department of Pathophysiology, School of Basic Medicine, China Medical University, Shenyang 110001, Liaoning Province, China. zhaochenghai1@sina.com
Telephone: +86-24-23256666-5362
Received: December 16, 2006
Revised: December 27, 2006
Accepted: January 26, 2007
Published online: April 21, 2007
Abstract

AIM: To identify the methylation of secreted frizzled-related protein 1 (SFRP1) in gastric cancer and to investigate the aberrant expression of SFRP1 and its correlation with the clinical pathological features of patients.

METHODS: We determined SFRP1 methylation and SFRP1 mRNA expression in 3 gastric cancer cell lines SGC-7901, BGC-823, HGC-27, from 52 primary gastric cancer specimens and matched tumor adjacent tissue specimens by methylation-specific (MSP) PCR and RT-PCR respectively. Fisher’s exact test was used to analyze the statistical association between clinical pathological data and aberrant expression of SFRP1.

RESULTS: In 3 cancer cell lines, BGC-823 and HGC-27 had methylated SFRP1 and lost SFRP1 mRNA expression. After treatment of BGC-823 and HGC-27 with the demethylating agent, 5-aza-2’-deoxycytidine, SFRP1 was re-expressed. In 52 primary gastric cancer specimens and matched tumor adjacent tissue specimens, hypermethylation of SFRP1 was detected in 23 (44%) and 8 (15%) specimens respectively (χ2 = 10.34, P < 0.01). Loss of SFRP1 expression was detected in 17(33%) and 6 (12%) specimens respectively (χ2 = 6.75, P < 0.01). There was a significant correlation between SFRP1 hypermethylation and SFRP1 expression loss. SFRP1 expression was also correlated significantly with tumor stage and lymph node status, but not with patient sex, age and histological type.

CONCLUSION: SFRP1 inactivation is a common and early event caused mainly by hypermethylation in gastric cancer. SFRP1 expression loss may be correlated with tumor metastasis in primary gastric cancer.

Keywords: Secreted frizzled-related protein 1, Wnt, Hypermethylation