期刊
CANCER
卷 112, 期 1, 页码 43-49出版社
WILEY
DOI: 10.1002/cncr.23135
关键词
somatostatin; hypermethylation; esophageal adenocarcinoma; esophageal squamous cell carcinoma; Barreft esophagus
类别
资金
- NCI NIH HHS [CA001808, CA85069, CA106763] Funding Source: Medline
- NIDDK NIH HHS [T32 DK067872] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [U01CA085069, R01CA001808, R21CA106763] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [T32DK067872] Funding Source: NIH RePORTER
BACKGROUND. The promoter of somatostatin (SST), a primary inhibitor of gastrin-stimulated gastric acid secretion, is hypermethylated in 80% of human colon cancers. The aim of the Current study was to investigate whether and at what stage promoter hypermethylation of SST is involved in human esophageal carcinogenesis. METHODS. SST promoter hypermethylation was examined by real-time methylation-specific polymerase chain reaction (PCR) (MSP) in 260 human esophageal tissue specimens. Real-time reverse-transcriptase PCR and MSP were also performed on esophageal cancer cell lines before and after treatment with 5-aza-2'deoxycytidine (5-Aza-dC). RESULTS. SST hypermethylation showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC) from normal esophagus (NE) (P <.01). Both SST methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett metaplasia without dysplasia or EAC (BE), low-grade and high-grade (HGD) dysplasia occurring in BE, FAC, and ESCC than in NE (P <.01). SST hypermethylation frequency was significantly lower in NE (9%) than in BE (70%), HGD (71.4%), or EAC (71.6%), whereas 14 (53.8%) of 26 ESCCs exhibited SST hypermethylation. There was a significant relation between SST hypermethylation and BE segment length, a known clinical risk factor for neoplastic progression. Demethylation of KYSE220 ESCC and OE33 EAC cells with 5-Aza-dC reduced SST methylation and increased SST rnRNA expression. SST rnRNA levels in native unmethylated EACs were significantly higher than in native methylated EACs (P <.05). CONCLUSIONS. SST promoter hypermethylation is a common event in human esophageal carcinomas and is related to early neoplastic progression in Barrett esophagus.
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