Promoter Methylation of Transforming Growth Factor-beta Receptor Type 1 Gene and Expression of TGF-β1 in Gastric Cardia Adenocarcinoma

ObjectiveTo investigated the relationships between the promoter methylation of transforming growth factor-beta receptor type 1 gene (TGFBR1）and protein expression of TGF-β1 and gastric cardia adenocarcinoma (GCA). MethodsMSP approach, RT-PCR and immunohistochemistry methods were used respectively to examine the methylation status of the 5' CpG island, mRNA and protein expression of TGFBR1 and TGF-β1 in tumors and corresponding normal tissues. ResultsThe prevalence TGFBR1 methylation was 34 /110 (30.9%) in tumor specimens, and significantly higher than that in corresponding normal tissues（P<0.01）. Methylation frequencies of stage Ⅲ and Ⅳ tumor tissues were significantly higher than those in stageⅠ andⅡtumor tissues（P<0.05）. TGFBR1 mRNA and protein expression of tumor tissues were significantly lower than that in corresponding normal tissues and was correlated with its methylation status. 72/110(65.5%) tumor tissues were demonstrated positive immunostaining of TGF-β1 and the frequency of positive protein expression of TGF-β1 was significantly higher than that in corresponding normal tissues（P<0.01）. The protein expression of TGF-β1 was significantly different among three differentiation groups of GCA（P<0.05）. The protein expression of TGFBR1 was inversely correlated with TGF-β1 in GCA. ConclusionPromoter hypermethylation of TGFBR1 and the higher protein expression of TGF-β1 might play important roles in gastric cardia adenocarcinoma.