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Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas.

Authors :
Wen XZ
Akiyama Y
Pan KF
Liu ZJ
Lu ZM
Zhou J
Gu LK
Dong CX
Zhu BD
Ji JF
You WC
Deng DJ
Source :
World journal of gastroenterology [World J Gastroenterol] 2010 Mar 14; Vol. 16 (10), pp. 1201-8.
Publication Year :
2010

Abstract

Aim: To understand the implication of GATA-4 and GATA-5 methylation in gastric carcinogenesis.<br />Methods: Methylation status of GATA-4 and GATA-5 CpG islands in human gastric mucosa samples, including normal gastric biopsies from 45 outpatients, gastric dysplasia [low-grade gastric intraepithelial neoplasia (GIN), n = 30; indefinite, n = 77], and 80 paired sporadic gastric carcinomas (SGC) as well as the adjacent non-neoplastic gastric tissues was analyzed by methylation specific polymerase chain reaction (MSP) and confirmed by denatured high performance liquid chromatography (DHPLC). Immunohistochemical staining was used to detect protein expression. The correlation between GATA-4 and GATA-5 methylation and clinicopathological characteristics of patients including Helicobacter pylori (H. pylori) infection was analyzed.<br />Results: GATA-4 and GATA-5 methylation was frequently observed in SGCs (53.8% and 61.3%, respectively) and their corresponding normal tissues (41.3% and 46.3%) by MSP. The result of MSP was consistent with that of DHPLC. Loss of both GATA-4 and GATA-5 proteins was associated with their methylation in SGCs (P = 0.01). Moreover, a high frequency of GATA-4 and GATA-5 methylation was found in both gastric low-grade GIN (57.1% and 69.0%) and indefinite for dysplasia (42.9% and 46.7%), respectively. However, GATA-4 and GATA-5 methylation was detected only in 4/32 (12.5%) and 3/39 (7.7%) of normal gastric biopsies. GATA-4 methylation in both normal gastric mucosa and low-grade GIN was also significantly associated with H. pylori infection (P = 0.023 and 0.027, two-sides).<br />Conclusion: Epigenetic inactivation of GATA-4 (and GATA-5) by methylation of CpG islands is an early frequent event during gastric carcinogenesis and is significantly correlated with H. pylori infection.

Details

Language :
English
ISSN :
2219-2840
Volume :
16
Issue :
10
Database :
MEDLINE
Journal :
World journal of gastroenterology
Publication Type :
Academic Journal
Accession number :
20222162
Full Text :
https://doi.org/10.3748/wjg.v16.i10.1201