Abstract
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, EAC, 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 mRNA expression. SST mRNA 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.
See also:
- Official Web Site: The Di Bella Method;
- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;
- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);
- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);
- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);
- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);
- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;
- Oesophageal squamocellular carcinoma: a complete and objective response;
- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;
- Complete objective response to biological therapy of plurifocal breast carcinoma;
- Neuroblastoma: Complete objective response to biological treatment.