Abstract:

[Abstract]   Objective  To investigate the aberrant methylation and expression of growth arrest and DNA-damage-in- ducible45gamma (GADD45G) gene in gastric cardia adenocarcinoma (GCA).  Methods  Bisulfite conversion-methylation specific polymerase chain reaction method (BS-MSP) and immunohistochemistry method were used respectively  to detect the methylation status and protein expression of GADD45G in138GCA tumor tissues and corresponding normal tissues.  Results  The methylation status of GADD45G distal promoter (region1) was not detected in GCA tumor tissues and corresponding normal tissues. For GADD45G region2and region3, the BS-MSP results of region 3were identical to that of region2. The methylation frequency of proximal promoter and exon 1in GADD45G island2(region2and region3) in GCA tumor tissues (49.3%,68/138) was significantly increased compared to that in corresponding normal tissues (0, P<0.01). The methylation status of this two sites in tumor tissues was associated with TNM stage of tumors (P<0.05). The protein expression of GADD45G in tumor tissues was significantly decreased than that in corresponding normal tissues (P<0.05)，and threre was a significant negative correlation with methylation status of GADD45G proximal promoter and exon1(rs=-0.398).  Conclusion   Thedecreased expression of GADD45G by hypermethylation of proximal promoter exon1of the gene may play an important role in gastric cardia adenocarcinoma.

Key words: cardia, adenocarcinoma, exons, DNA methylation, immunohistochemistry, growth arrest and DNA-damage-inducible 45 gamma