Hypermethylation and aberrant expression of Wnt antagonist secreted frizzled-related protein 1 in gastric cancer.

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 (chi(2) = 10.34, P < 0.01). Loss of SFRP1 expression was detected in 17(33%) and 6 (12%) specimens respectively (chi(2) = 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.