Methylation status of DACT-1 gene and its clinical significance in gastric cardia adenocarcinoma
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Abstract:
Objective:To detect the methylation status of dishevelled-binding antagonist of beta-catenin 1 (DACT-1) gene in gastric cardia adenocarcinoma (GCA) tissues and adjacent non-cancerous tissues, and to study its clinical significance. Methods: Methylation specific PCR (MSP) and quantitative RT-PCR were respectively applied to examine the CpG methylation of the DACT-1 gene and expression of its mRNA in tumor tissues and corresponding adjacent noncancerous tissues of 112 samples (collected from Department of Surgery, the Fourth Hospital Affiliated to Hebei Medical University and Department of Thoracic Surgery, Cixian Cancer Hospital during 2006 to 2014). Results: Methylation rates of DACT-1 gene in the GCA tissues and the adjacent noncancerous tissues were 51.8% (58/112) and 17.6% (20/112) respectively, indicating that methylation rate of DACT-1 in the GCA tissues was significantly higher than that in the noncancerous tissues (P<0.01). Expression of DACT-1 mRNA in the cancer tissues was 0.580±0.143, which was significantly lower than that in the adjacent noncancerous tissues (0.654±0.110,P<0.01). Expression of DACT-1 mRNA in the GCA tissues with methylated DACT-1 was 0.488±0.097, which was obviously lower than that in the GCA tissues with unmetylated ACT-1 (0.675±0.120), and the methylation status of the gene was significantly related with expression of its mRNA(P<0.01). The hypermethylation of DACT-1 gene in the GCA tissues was significantly related with lymph node metastasis and family history of upper gastrointestinal cancer (P<0.05), but not related with age, gender, pathological grading and clinical staging of the cancer patients(P>0.05). Conclusion: The hypermethylation of CpG in DACT-1 3gene might be one of the mechanisms causing down-regulation of DACT-1 expression. The methylation status of promoter area in DACT-1 gene is expected to provide a novel indicator for the clinical diagnosis and prognosis evaluation of GCA.
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Project supported by Natural Science Foundation of Hebei Province (No. H2013206315) and Program of Medical Science Research Key Subject of Hebei Province (No. 20130543)