Methylation status of IGFBP7 gene in human gastric cardia adenocarcinoma tissues
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Abstract:
Objective:To investigate the promoter and exon1 methylation of insulin-like growth factor binding protein 7 ( IGFBP7 ) gene and its correlation with the expression of IGFBP7 protein in gastric cardia adenocarcinoma (GCA) tissues. Methods: Eighty-five GCA samples and 67 paracancerous tissues from GCA patients (who had been diagnosed in the Forth Hospital of Hebei Medical University, from April, 2009 to December, 2011) were included in the present study. Methylation specific polymerase chain reaction (MSP), RT-PCR and immunohistochchemistry methods were respectively used to examine the methylation status, mRNA and protein expressions of IGFBP7 in GCA tissues and paracancerous tissues. Results: For the promoter site, the methylation frequency of IGFBP7 gene in the GCA specimens (52.9%, 45/85) was significantly higher than that in the paracancerous tissues (35.8%, 24/67) (P<005). For the 5′ UTR of exon1, the methylation frequency of IGFBP7 gene in the GCA specimens (35.3%, 30/85) was significantly higher than that in the paracancerous tissues (19.4%, 13/67) (P<0.05). The methylation frequency of IGFBP7 gene in the promoter site was significantly higher than that in the 5′ UTR of exon1 (P<0.05). The mRNA and protein expressions of IGFBP7 in the GCA tissues were significantly higher than those in the paracancerous tissues (P<0.05) and were inversely correlated with the methylation status of promoter. Conclusion: Compared to the exon1, IGFBP7 promoter site is more likely to be methylated in GCA tissues and may play an important role in the down-regulation of IGFBP7 in GCA tumorigenesis. Hypermethylation of IGFBP7 in promoter site may be one of the mechanisms leading to the occurrence of GCA.
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Project supported by the Science and Technology Program of Hebei Department of Science and Technology (No. 072761223)