Alteration in Methylation Pattern of Retinoblastoma 1 Gene Promotor Region in Intestinal Metaplasia with or without Helicobacter pylori and Gastric Cancer Patients

Boyacioglu, Sedat; Kasap, Elmas; Yüceyar, Hakan; Korkmaz, Mehmet

doi:10.17219/acem/38842

Cited by 7 publications

(9 citation statements)

References 20 publications

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“…Promoter methylation of ASC/TMS1 is associated with poor prognosis of patients with gastric cancer [68]. RBL1 is methylated in patients with intestinal metaplasia, with or without Helicobacter pylori , and in gastric cancer patients [69]. Promoter methylation of RNF180 is associated with Helicobacter pylori infection and serves as a marker for gastric cancer and atrophic gastritis [70].…”

Section: Discussionmentioning

confidence: 99%

Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies

et al. 2017

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Clinically useful molecular tools to triage gastric cancer patients are not currently available. We aimed to develop a molecular tool to predict gastric cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer clinics in low resource settings.We discovered and validated a DNA methylation biomarker panel in endoscopic samples obtained from 362 patients seen between 2004 and 2009 in three high-risk gastric cancer clinics in Lima, Perú, and validated it in 306 samples from the Cancer Genome Atlas project (“TCGA”). Global, epigenome wide and gene-specific DNA methylation analyses were used in a Phase I Biomarker Development Trial to identify a continuous biomarker panel that combines a Global DNA Methylation Index (GDMI) and promoter DNA methylation levels of IRF4, ELMO1, CLIP4 and MSC.We observed an inverse association between the GDMI and histological progression to gastric cancer, when comparing gastritis patients without metaplasia (mean = 5.74, 95% CI, 4.97−6.50), gastritis patients with metaplasia (mean = 4.81, 95% CI, 3.77−5.84), and gastric cancer cases (mean = 3.38, 95% CI, 2.82−3.94), respectively (p < 0.0001). Promoter methylation of IRF4 (p < 0.0001), ELMO1 (p < 0.0001), CLIP4 (p < 0.0001), and MSC (p < 0.0001), is also associated with increasing severity from gastritis with no metaplasia to gastritis with metaplasia and gastric cancer.Our findings suggest that IRF4, ELMO1, CLIP4 and MSC promoter methylation coupled with a GDMI>4 are useful molecular tools for gastric cancer risk stratification in endoscopic biopsies.

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Section: Discussionmentioning

confidence: 99%

Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies

et al. 2017

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“…However, there was no significant difference in the rates of H. pylori infection either between IGC and DGC, or between proximal and distal tumors ( 139 ). Interestingly, high levels of RB methylation in H. pylori -positive individuals might increase the risk of GC ( 140 ). The proportions of RB tumor suppressor and the p53 tumor suppressor pathway abnormalities in H. pylor i-infected GC were higher than that in non- H. pylori -infected GC ( 42 ).…”

Section: Helicobacter Pylori and The Rb And P53 Tumor Suppressor Systemsmentioning

confidence: 99%

The Role and Clinical Implications of the Retinoblastoma (RB)-E2F Pathway in Gastric Cancer

2021

Front. Oncol.

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Gastric cancer is the most common malignant tumor in the digestive tract, with very high morbidity and mortality in developing countries. The pathogenesis of gastric cancer is a complex biological process mediated by abnormal regulation of proto-oncogenes and tumor suppressor genes. Although there have been some in-depth studies on gastric cancer at the molecular level, the specific mechanism has not been fully elucidated. RB family proteins (including RB, p130, and p107) are involved in cell cycle regulation, a process that largely depends on members of the E2F gene family that encode transcriptional activators and repressors. In gastric cancer, inactivation of the RB-E2F pathway serves as a core transcriptional mechanism that drives cell cycle progression, and is regulated by cyclins, cyclin-dependent kinases, cyclin-dependent kinase inhibitors, p53, Helicobacter pylori and some other upstream molecules. The E2F proteins are encoded by eight genes (i.e. E2F1 to E2F8), each of which may play a specific role in gastric cancer. Interestingly, a single E2F such as E2F1 can activate or repress transcription, and enhance or inhibit cell proliferation, depending on the cell environment. Thus, the function of the E2F transcription factor family is very complex and needs further exploration. Importantly, the presence of H. pylori in stomach mucosa may affect the RB and p53 tumor suppressor systems, thereby promoting the occurrence of gastric cancer. This review aims to summarize recent research progress on important roles of the complex RB-E2F signaling network in the development and effective treatment of gastric cancer.

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“…The cancer-free control subjects were recruited among those who had applied to the gastroenterology outpatient clinic with symptoms such as epigastric pain, bloating, early satiation, fullness, epigastric burning, nausea, and vomiting but their endoscopical, radiological, and pathological examinations had been found normal. The study groups were formed and included in the current study based on the same inclusion and exclusion criteria in the studies of ORENAY-BOYACIOGLU et al (2016) and ASIK-SEN et al (2012). All information regarding to age, gender, personal, and familial history of the study subjects were recorded in individual interviews with the subjects.…”

Section: Cases Endoscopy and Tissue Samplesmentioning

confidence: 99%

“…Genomic DNA was isolated from the gastric mucosa biopsy specimens using QIAamp DNA blood mini kit (Qiagen, Hilden, Germany) according to ORENAY-BOYACIOGLU et al (2016) and ASIK-SEN et al (2012), and stored at -20°C. The DNA samples were quantified using Nanodrop 1000 (Nanodrop, Wilmington, DE, USA) and the DNA samples with A260/A280 ratio between 1.8-2.0 were considered satisfactory for further steps.…”

Section: Dna Isolationmentioning

confidence: 99%

Association of interleukin 12B rs3212227 polymorphism with gastric cancer, intestinal metaplasia, and helicobacter pylori infection

et al. 2020

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Interleukin 12 (IL-12) has a key function in promoting Th1 immune response in the gastrointestinal mucosa. Although cytokine gene polymorphisms are associated with increased risk of gastric cancer (GC), studies on different geographic regions and ethnic groups are not able to draw a consistent result. The current case-control study aims to find out an association between a functional IL-12B rs3212227 polymorphism and the susceptibility and clinical features of the study groups, which are GC, Helicobacter pylori-infected and H. pylori-uninfected intestinal metaplasia (IM). In this study, IL-12B rs3212227 polymorphism was genotyped in 35 GC cases, 25 H. pylori-infected IM patients, 25 H. pylori-uninfected IM patients, and 25 control subjects. PCR-RFLP analysis was performed to find out and compare the polymorphism profiles of case biopsies. There was statistical significance in genotype distributions and allelic frequencies in GC patients with proximal arrest in stomach (p=0.042). The rs3212227 genotypes and allelic frequencies were not correlated with any of the study groups (p>0.05). Other clinical features examined in the GC patients were also not correlated with the rs3212227 genotypes and allelic frequencies (p>0.05). Current findings suggest that IL-12B rs3212227 polymorphism may play a role in GC development.

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Alteration in Methylation Pattern of Retinoblastoma 1 Gene Promotor Region in Intestinal Metaplasia with or without Helicobacter pylori and Gastric Cancer Patients

Cited by 7 publications

References 20 publications

Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies

Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies

The Role and Clinical Implications of the Retinoblastoma (RB)-E2F Pathway in Gastric Cancer

Association of interleukin 12B rs3212227 polymorphism with gastric cancer, intestinal metaplasia, and helicobacter pylori infection

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