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Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies.
- Source :
-
Oncotarget [Oncotarget] 2017 Jun 13; Vol. 8 (24), pp. 38501-38516. - Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Adenocarcinoma genetics
Adolescent
Adult
Aged
Aged, 80 and over
Basic Helix-Loop-Helix Transcription Factors genetics
Biopsy
Carrier Proteins genetics
DNA Methylation genetics
Female
Gastroscopy
Genome-Wide Association Study
Humans
Interferon Regulatory Factors genetics
Male
Membrane Proteins
Middle Aged
Stomach Neoplasms genetics
Young Adult
Adenocarcinoma diagnosis
Biomarkers, Tumor genetics
Early Detection of Cancer methods
Stomach Neoplasms diagnosis
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 8
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 28418867
- Full Text :
- https://doi.org/10.18632/oncotarget.16258