Abstract: OBJECTIVE: We investigated the promoter methylation of secreted frizzled-related protein 4(SFRP4) and SFRP5 gene in gastric cardia adenocarcinoma (GCA). METHODS: Methylation specific PCR (MSP) method was used to examine the methylation status of the 5' CpG island of SFRP4 and SFRP5 genes in 94 tumors and 47 corresponding normal tissues. RESULTS: Methylation frequencies of SFRP4 and SFRP5 genes in tumors were 68.1％(64/94)and 79.8％(75/94), respectively, significantly higher than that in corresponding normal tissues (8.5％ and 12.8％, respectively)(P<0.01). Methylation frequencies of SFRP4 in poor differentiation group (92.6％,50/54)was significantly higher than that in moderate and poor-moderate differentiation groups (35％,14/40). Methylation frequencies of SFRP5 in lymph node metastasis group (89.3％,50/56) was significantly higher than that in no lymph node metastasis group (65.8％,25/38). Methylation frequencies of SFRP5 in poor differentiation group was higher than that in moderate and poor-moderate differentiation groups, and SFRP4 in lymph node metastasis group was higher than that in no lymph node metastasis group but without significant difference(P>0.05). 57 cases of GCA showed simultaneous methylation of SFRP4 and SFRP5 genes, including 18 moderate and poor-moderate differentiation tumors, and 39 moderate differentiation tumors. Simultaneous methylation frequencies of SFRP4 and SFRP5 genes in moderate andpoor-moderate differentiation groups was significantly lower than that in moderate group. CONCLUSION: SFRP4 and SFRP5 genes might be associated with oncogenanesis of GCA and hypermethylation of these genes might be related to the malignant behavior of GCA.

Key words: gastric cardia adenocarcinoma, methylation, secreted frizzled related protein 4, secreted frizzled related protein 5