DNA Methylation as a Molecular Biomarker in Gastric Cancer

Tahara, Tomomitsu; Arisawa, Tomiyasu

doi:10.2217/epi.15.4

Cited by 134 publications

(98 citation statements)

References 83 publications

(135 reference statements)

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“…and a separate one based on methylation in non-neoplastic inflamed/aged tissues ( ER , CDH13 , MYOD1 , SFRP1 , P2RX7 , IGF2 , N33 , MIR124A1 , MIR124A3 etc.) [24]. We also evaluated the methylation status of the LINE1 repetitive element using bisulfite pyrosequencing.…”

Section: Methodsmentioning

confidence: 99%

Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa

et al. 2016

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BackgroundTelomere length shortening in Helicobacter pylori (H. pylori) infected gastric mucosa constitutes the earliest steps toward neoplastic transformation. In addition to this genotoxic changes, epigenetic changes such as promoter CpG island (PCGI) methylation are frequently occurred in H. pylori infected gastric mucosa. The aim of this study was to investigate a potential link between H. pylori related PCGI methylation and telomere length shortening in the human gastric mucosa.MethodsTelomere length was measured in non-neoplastic gastric mucosa from 106 cancer-free subjects. To identify H. pylori related PCGI methylation, bisulfite pyrosequencing was used to quantify the methylation of 49 PCGIs from 47 genes and LINE1 repetitive elementResultsWe identified five PCGIs (IGF2, SLC16A12, SOX11, P2RX7 and MYOD1), which the methylation is closely associated with H. pylori infection. Hypermethylation of all these PCGIs was associated with development of pathological state from normal to mild, active, and atrophic gastritis (P<0.001) and lower pepsinogen I/II ratio (P<0.05), an indicator for gastric mucosal atrophy. Telomere shortening was significantly associated with mean Z score methylation of five PCGIs (R=−0.39, P<0.0001) and four of these locus (IGF2: R=−0.35, P=0.0003, SLC16A12: R=−0.35, P=0.0002, P2RX7: R=−0.29, P=0.003, and MYOD1: R=−0.33, P=0.0005). Multivariate analysis revealed that telomere shortening held an increased risk for hypermethylation (odds ratio: 1.71, 95% confidence interval: 1.11-2.63, P=0.016).ConclusionPotential link between H. pylori related PCGI methylation and telomere shortening emphasize the importance of genotoxic-epigenetic interaction in the pathological state of H. pylori infected gastric mucosa.

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Section: Methodsmentioning

confidence: 99%

Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa

et al. 2016

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“…And the majority (about 90%) of gastric cancer belongs to the pathological subtype of adenocarcinoma [3]. Surgical resection remains the primary treatment for gastric cancer; however, the five-year survival rate for late stage gastric cancer rarely exceeds 5% [4, 5]. Tumor node metastasis (TNM) staging classification is the most common tool in the prediction of gastric cancer prognosis.…”

Section: Introductionmentioning

confidence: 99%

NDRG4 hypermethylation is a potential biomarker for diagnosis and prognosis of gastric cancer in Chinese population

et al. 2016

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In order to assess whether N-Myc downstream regulated gene 4 (NDRG4) methylation was associated with the diagnosis and prognosis of gastric cancer, we measured the methylation of NDRG4 promoter and gene body regions among 110 gastric cancer patients using quantitative methods (MethyLight and pyrosequencing). Both NDRG4 promoter and gene body methylation levels were increased in tumor tissues than paired adjacent normal tissues (P < 0.001). NDRG4 gene body methylation was found to be significantly associated with age and tumor differentiation. NDRG4 promoter hypermethylation was proved to be a predictor of poor overall survival. However, opposite result was observed among The Cancer Genome Atlas (TCGA) cohort. The findings from gastric cell lines and public databases have suggested that NDRG4 methylation level was inversely associated with NDRG4 transcription level. Subsequent luciferase reporter gene assay showed that promoter CpG island but not gene body CpG island was able to upregulate gene expression. Collectively, NDRG4 promoter hypermethylation contributed to the risk of gastric cancer and predicted a poor prognosis in Chinese gastric cancer patients. Moreover, the combined methylation levels of NDRG4 promoter and gene body served as diagnostic biomarkers in gastric cancer.

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“…However, the highly expensive and relatively complex operating procedures make these methods unsuitable for screening on a population basis, particularly for asymptomatic subjects. So, the ideal gastric cancer screening or early diagnosis methods should be of high sensitivity, high specificity, cheap, non-invasive, and easy to operate [13]. Serum biomarkers are easy to access and widely used for GC diagnoses such as CEA, CA19-9, CA72-4, etc.…”

Section: Discussionmentioning

confidence: 99%

Increased miR-25 expression in serum of gastric cancer patients is correlated with CA19-9 and acts as a potential diagnostic biomarker

et al. 2017

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AbstractObjectiveTo evaluate miR-25 expression in serum of gastric cancer (GC) patients and whether it can be a potential biomarker for GC diagnosis.MethodsForty one pathology confirmed GC patients and 41 healthy controls were included in this study. 10 mL peripheral venous blood were collected from GC patients and healthy controls. miR-25 relative expression and CA19-9 level in serum of GC patients and healthy controls were measured by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme linked immunosorbent assay (ELISA), respectively. The diagnostic sensitivity, specificity and receiver operating characteristic (ROC) curve of serum miR-25 and CA19-9 were calculated by STATA11.0 software.ResultsThe relative expression of miR-25 was 0.47±0.53 and 0.05±0.36 in serum of GC patients and healthy controls respectively with significant statistical difference (P<0.05). The serum level of CA19-9 for GC patients and healthy controls were 11.91±6.17 U/mL and 7.40±3.97 U/mL, indicating GC patients were much higher than those of healthy controls (P<0.05). The diagnostic sensitivity and specificity were 78.05% and 60.98% with the cut-off value of 0.32 for serum miR-25. Under this cut-off value, the area under the ROC curve was 0.75. For serum CA19-9, the diagnostic sensitivity and specificity were 70.73% and 56.10% with the cut-off value of 9.22 U/mL. Under this cut-off value, the area under the ROC curve was 0.73 with the 95% confidence interval of 0.62-0.84. Positive correlation was found between serum miR-25 relative expression and CA19-9 concentration of GC patients (r=0.75, P<0.05).ConclusionAccording to our present study, serum miR-25 was elevated in GC patients which may serve as a diagnostic biomarker for GC.

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DNA Methylation as a Molecular Biomarker in Gastric Cancer

Cited by 134 publications

References 83 publications

Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa

Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa

NDRG4 hypermethylation is a potential biomarker for diagnosis and prognosis of gastric cancer in Chinese population

Increased miR-25 expression in serum of gastric cancer patients is correlated with CA19-9 and acts as a potential diagnostic biomarker

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