Site-Specific Hypermethylation of SST 1stExon as a Biomarker for Predicting the Risk of Gastrointestinal Tract Cancers

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Published on Monday, 14 March 2022

Abstract

Background: DNA methylation is an important epigenetic modification in tumorigenesis, and similar epigenetic regulation mechanisms have been found in the gastrointestinal tract (GIT) cancers. Somatostatin (SST) has been confirmed to be expressed throughout the GIT. This study aimed to simultaneously explore the relationships between the SST methylation and the risks of three GIT cancers (esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC)) and to evaluate its diagnostic value.

Methods: Differentially methylated regions (DMRs) of the SST gene, including TSS200, 1stExon, and the gene body, were identified in GIT cancers by The Cancer Genome Atlas (TCGA) database analysis. Further analyses were conducted in tissue samples of EC (n = 50), GC (n = 99), and CRC (n = 80). The SST methylation was detected by bisulfite-sequencing PCR (BSP), and the SST expression was detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR).

Results: In GIT cancers, DMR-related CpG islands were mainly located in the 1stExon. The methylation status of the SST 1stExon in the tumor tissues was significantly higher than that in the adjacent noncancerous tissues, and the methylation rates of the specific CpG sites were correlated with clinical phenotypes. The average methylation rate (AMR) of the SST 1stExon was negatively correlated with the SST gene expression in GC and CRC (both P < 0.001). For the diagnosis of GIT cancers, the combined detection of methylation at CpG sites +18 and +129 showed the highest area under the curve (AUC 0.698), with a sensitivity of 59.3% and a specificity of 72.8%.

Conclusions: The site-specific hypermethylation of the SST 1stExon increases the risk of GIT cancers and might be a potential predictive marker for pan-GIT cancers.

 



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See also:

- Official Web Site: The Di Bella Method;

 

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- 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, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (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);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

 

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response.