Methylation and mRNA expression of WWOX and smad 4 gene in gastric cardia adenocarcinoma

Methylation status at the promoter regions of WWOX and Smad4 gene and their expression in gastric cardia adenocarcinoma (GCA) were investigated. And their relationship with the development of GCA and the possible mechanism were also discussed. The methylation status of WWOX and Smad4 gene and their mRNA expression levels in the GCA and the corresponding normal mucosal tissues were investigated by nested methylation specific PCR (MSP) and RT-PCR, respectively. Methylation rate of WWOX gene in the GCA and para-carcinoma tissues was 26.1% and 4.2%, respectively, with significant difference (P < 0.05); methylation rate of WWOX gene in the GCA patients of stage III/IV (43.3%) was higher than that in the patients of stage I/II (12.8%), with significant difference (P = 0.004). The relative expression level of WWOX mRNA in the GCA and para-carcinoma tissues was 0.77±0.16 and 0.89±0.12, respectively, with significant difference (P < 0.05); the relative expression level of Smad4 mRNA in the GCA and the para-carcinoma tissues was 0.75±0.17 and 0.88±0.14, respectively, showing significant difference (P < 0.05). WWOX gene methylation probably contributes to pathogenesis of GCA and promotes progression of GCA.