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Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas.
- 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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Carcinoma metabolism
Carcinoma microbiology
CpG Islands
DNA Methylation
Female
GATA4 Transcription Factor metabolism
GATA5 Transcription Factor metabolism
Helicobacter Infections complications
Helicobacter pylori
Humans
Male
Middle Aged
Promoter Regions, Genetic
Stomach Neoplasms metabolism
Stomach Neoplasms microbiology
Carcinoma genetics
GATA4 Transcription Factor genetics
GATA5 Transcription Factor genetics
Stomach Neoplasms genetics
Subjects
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