Methylation status of Caveolin-1 gene and its relationship with ectopic expression of β-catenin in gastric cardia adenocarcinoma

Objective: To detect the methylation status of Wnt pathway-related factor Caveolin-1 gene in gastric cardia adenocarcinoma (GCA) and adjacent non-cancerous tissues, and to explore the impact of Caveolin-1 gene methylation on the expressions of its mRNA and protein and β-catenin, a central factor of Wnt pathway. Methods: The methylation status of Caveolin-1 gene in GCA and the corresponding adjacent non-cancerous tissues from 138 patients was detected by methylation-specific PCR (MSP), and the relationship of methylation status of this gene with the clinicopathological features of GCA patients was analyzed. The expressions of Caveolin-1 mRNA in GCA and the corresponding adjacent non-cancerous tissues were detected by reverse transcription-PCR (RT-PCR). The expressions of Caveolin-1 protein and β-catenin were detected by immunohistochemistry. The correlations of methylation status of Caveolin-1 gene with the expressions of Caveolin-1 mRNA and protein and the ectopic expression of β-catenin protein were further analyzed by Spearman rank correlation test. Results: In the GCA tissues, the frequency of Caveolin-1 gene methylation was 26.1% (36/138), which was significantly higher than that in the corresponding adjacent non-cancerous tissues (P 0.05). The positive-expression rates of Caveolin-1 mRNA and protein were 48.6% and 32.6%, respectively, which were both lower than those in the corresponding adjacent non-cancerous tissues (P < 0.01). The ectopic expression frequencies of β-catenin protein were 87.7% and 39.9% in GCA and the corresponding adjacent non-cancerous tissues, respectively; there was a significant difference between the two groups (P < 0.01). The expressions of Caveolin-1 mRNA and protein and the ectopic expression of β-catenin protein were significantly correlated with the methylation status of Caveolin-1 gene in GCA tissues (P < 0.05). Conclusion: The CpG methylation is one of the mechanisms causing Caveolin-1 gene silencing in GCA. Caveolin-1 gene methylation may play an important role in occurrence of GCA through aberrantly activated Wnt/β-catenin signaling pathway. DOI:10.3781/j.issn.1000-7431.2014.09.008