Aberrant Promoter Methylation Of SFRPs-the Antagonists Of Wnt In Gastric Cardia Adenocarcinoma

Objective: Gastric cardia adenocarcinoma(GCA) is a especial type of esophagogastric junction cancer which was one of the frequent kind of digestive system malignant tumour, and there was a increasing tendency between morbility and mortality. In recent years, with the endoscopic technique in high-incidence area of esophageal cancer screening in the extensive application, there found a high incidence of esophageal cancer at the same high incidence of GCA exist, about 70 / 100000. The disease incidence of hidden When symptoms are advanced. It is necessary to conduct a study of its pathogenesis, in order to reduce the GCA morbidity and mortality.Recently, the DNA methylation has been the hot spot. The purpose of this study was to investigate the methylation of gene SFRP1, SFRP2, SFRP4 and SFRP5 in GCA and corresponding normal tissues, and we tried to explore the relationship between gene methylation and the carcinogenesis, infiltration, metastasis and pathological differentiation of GCA, and provide a new theory and experiment evidence for pathogenesy, gene therapy and immunotherapy, clinical prognosis of gastric cardia carcinoma.Methods1 We used a methylation specific PCR (MSP) method to examine the methylation status of the 5' CpG island of SFRP1, SFRP2, SFRP4 and SFRP5 gene in tumors and corresponding normal tissues.2 SPSS11.5 was applied to analyze the results of experiment.Results1 SFRP1 gene was methylated in 82 of 94 (87.2%) tumor specimens, which was significantly higher than that in corresponding normal tissues14.9% (7/47) (P<0.001). Methylation frequencies of SFRP1 in lymph node metastasis group 96.4% was significantly higher than that in no lymph node metastasis group 73.7%. Methylation frequencies of SFRP1 gene in poor differentiation group 90.7% (49/54) was higher than moderate and poor-moderate differentiation groups 82.5% (33/40) , but did not show significant difference (P>0.05) . Methylation frequencies of SFRP1 gene had difference in different age and gender groups, but no significance (P>0.05).2 SFRP2 gene was methylated in 78 of 94 (83%) tumor specimens, which was significantly higher than that in corresponding normal tissues 55.3% (26/47) (P<0.001). Methylation frequencies of SFRP2 in lymph node metastasis group 85.7% was higher than that in no lymph node metastasis group 78.9%,Methylation frequencies of SFRP2 gene in poor differentiation group 88.9% was higher than moderate and poor-moderate differentiation groups 75%, but all did not show significant difference (P>0.05). Methylation frequencies of SFRP2 gene had difference in different age and gender groups, but no significance (P>0.05).3 SFRP4 gene was methylated in 64 of 94 (83%) tumor specimens, which was significantly higher than that in corresponding normal tissues 8.5% (4/47). Methylation frequencies of SFRP4 gene in poor differentiation group 92.6% (50/54) was significantly higher than moderate and poor-moderate differentiation groups 35% (14/40) (P<0.001). Methylation frequencies of SFRP4 in lymph node metastasis group 73.2% was higher than that in no lymph node metastasis group 60.5%, but did not show significant difference (P>0.05). Methylation frequencies of SFRP4 gene had difference in different age and gender groups, but no significance (P>0.05).4 SFRP5 gene was methylated in 75 of 94 (79.8%) tumor specimens, which was significantly higher than that in corresponding normal tissues 12.8% (4/47). Methylation frequencies of SFRP5 in lymph node metastasis group 89.3% was significantly higher than that in no lymph node metastasis group 65.8%. Methylation frequencies of SFRP5 gene in poor differentiation group 85.1% was higher than moderate and poor-moderate differentiation groups 72.5%, but did not show significant difference (P>0.05). Methylation frequencies of SFRP5 gene had difference in different age and gender groups, but no significance (P>0.05).Conclusions1 The methylation frequencies of SFRP1, SFRP2, SFRP4 and SFRP5 in GCA were all significantly higher than that in corresponding normal tissues, indicating that the methylation of SFRP1, SFRP2, SFRP4 and SFRP5 gene may be related with oncogenesis of GCA.2 The methylation frequencies of SFRP1, SFRP5 gene in lymph node metastasis group and no lymph node metastasis group has significant difference, indicating that SFRP1 and SFRP5 gene may be related with invasion of GCA. Methylation frequencies of SFRP4 gene in poor differentiation group was significantly higher than that in moderate and poor-moderate differentiation groups, which indicated that SFRP4 may related with malignant biological behavior of GCA.