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Archive > Volume 20 Issue 3 > 2013,20(3):317-322. DOI:10.3872/j.issn.1007-385X.2013.03.011 Prev Next
Clinical Research
Expression and aberrant methylation of growth arrest and DNA-damage-inducible 45 alpha gene in human gastric cardia adenocarcinoma tissues and its clinical significance
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Abstract:
Objective:To investigate the expression and aberrant methylation of growth arrest and DNA-damage-inducible 45 alpha ( GADD45A ) gene in gastric cardia adenocarcinoma (GCA) and to explore its clinical significance. Methods: Tissue samples in GCA patients (138 cases) were selected from Fourth Hospital of Hebei University during 2004 to 2007. Bisulfite sequencing (BS-Seq), bisulfite conversion-methylation specific polymerase chain reaction (BS-MSP), reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry methods were used respectively to detect the methylation status, mRNA and protein expression of GADD45A gene in GCA tissues and the para-carcinoma normal tissues. Results: The methylation frequency of four CpG sites in distal promoter of GADD45A in GCA tissues (44.93%, \[62/138\]) was significantly higher than that in the para-carcinoma normal tissues (0.00%, 0/138) (P<0.01). The methylation frequency of 4 CpG sites in stage Ⅲ and Ⅳ GCA tissues was significantly higher than that in stage Ⅰ and Ⅱ GCA tissues (P<0.05). However, the methylation status GADD45A in GCA tissues was not correltaed with age, gender and pathological differentiation (P>0.05). For GADD45A region 2 and 3 located in proximal promoter and exon 1, no methylation was detected in GCA and the para-carcinoma normal tissues. The expression of GADD45A mRNA and positive expression rate of GADD45A protein in GCA tissues were significantly lower than those in the para-carcinoma normal tissues (\[0.35±0.15\] vs \[0.78±0.26\], 42.75% vs 71.01%, P<0.05) and was associated with methylation status of 4 CpG sites in distal promoter (r=-0.52, P<0.01). Conclusion:Hypermethylation of four CpG sites in distal promoter of GADD45A gene may be responsible for the decreased expression of GADD45A in GCA.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81101854), and the Science and Technology y Bureau of Hebei Province（No.072761223）
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