Methylation of apoptosis protease activating factor-1 gene in gastric cardia adenocarcinoma and its clinical significance
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Abstract:
Objective : To investigate the methylation of apoptosis protease activating factor-1 ( Apaf-1) gene promoter and its correlation with protein expression of enhancer of zeste homolog 2 (EZH2) in gastric cardia adenocarcinoma (GCA). Methods: Methylation specific polymerase chain reaction (MSP) method was used to examine the methylation status of Apaf-1 gene, and immunohistochemistry method was used to detect the protein expression of Apaf-1 and EZH2 in GCA and paracancerous tissues. Results: The frequency of Apaf-1 methylation in GCA tissues (49.6%, 62/125) was significantly higher than that in paracancerous tissues (4.0%, 5/125, P<0.01). The methylation frequencies of Apaf-1gene in stage Ⅲ and Ⅳ GCA tissues were significantly higher than those in stage Ⅰ and Ⅱ GCA tissues (58.8% vs 38.6%, P<0.05). No significant difference in the methylation frequency of Apaf-1 gene was found in three histological differentiated groups (P>0.05). The positive protein expression of Apaf-1 in GCA tissues was significantly decreased compared with paracancerous tissues (39.2% vs 96.0%, P<0.01) and was correlated with its methylation status. The positive protein expression of EZH2 in GCA tissues was significantly increased compared with that in paracancerous tissues (744% vs 11.2%, P<0.01) and was negatively correlated with the expression of Apaf-1 protein in GCA. Conclusion: The promoter of Apaf-1 gene is hypermethylated and both Apaf-1 and EZH2 may play important roles in the development of GCA.
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Project supported by the Key Project in Medical Scientific Research of Hebei Province (No. 20090465)