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

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dc.contributor.author Pirini, Francesca
dc.contributor.author Noazin, Sassan
dc.contributor.author Jahuira-Arias, Martha H.
dc.contributor.author Rodriguez-Torres, Sebastian
dc.contributor.author Friess, Leah
dc.contributor.author Michailidi, Christina
dc.contributor.author Cok, Jaime
dc.contributor.author Combe, Juan
dc.contributor.author Vargas, Gloria
dc.contributor.author Prado, William
dc.contributor.author Soudry, Ethan
dc.contributor.author Perez, Jimena
dc.contributor.author Yudin, Tikki
dc.contributor.author Mancinelli, Andrea
dc.contributor.author Unger, Helen
dc.contributor.author Ili-Gangas, Carmen
dc.contributor.author Brebi-Mieville, Priscilla
dc.contributor.author Berg, Douglas E.
dc.contributor.author Hayashi, Masamichi
dc.contributor.author Sidransky, David
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Guerrero-Preston, Rafael
dc.date.accessioned 2019-01-25T15:18:34Z
dc.date.available 2019-01-25T15:18:34Z
dc.date.issued 2017
dc.identifier.uri https://hdl.handle.net/20.500.12866/4642
dc.description.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, Peru, 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. en_US
dc.language.iso eng
dc.publisher Impact Journals
dc.relation.ispartofseries Oncotarget
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Adolescent en_US
dc.subject Adult en_US
dc.subject Female en_US
dc.subject Humans en_US
dc.subject Male en_US
dc.subject Young Adult en_US
dc.subject Aged en_US
dc.subject Middle Aged en_US
dc.subject Aged, 80 and over en_US
dc.subject Biopsy en_US
dc.subject Genome-Wide Association Study en_US
dc.subject Biomarkers, Tumor/genetics en_US
dc.subject Adaptor Proteins, Signal Transducing/genetics en_US
dc.subject Adenocarcinoma/diagnosis/genetics en_US
dc.subject Basic Helix-Loop-Helix Transcription Factors/genetics en_US
dc.subject Carrier Proteins/genetics en_US
dc.subject DNA Methylation/genetics en_US
dc.subject Early Detection of Cancer/methods en_US
dc.subject ELMO1 en_US
dc.subject epigenome-wide DNA methylation analysis en_US
dc.subject Gastroscopy en_US
dc.subject global DNA methylation index en_US
dc.subject Interferon Regulatory Factors/genetics en_US
dc.subject IRF4 en_US
dc.subject Stomach Neoplasms/diagnosis/genetics en_US
dc.subject translational epigenomics en_US
dc.title Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.18632/oncotarget.16258
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.21
dc.relation.issn 1949-2553


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