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Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies.
Pirini, Francesca; Noazin, Sassan; Jahuira-Arias, Martha H; Rodriguez-Torres, Sebastian; Friess, Leah; Michailidi, Christina; Cok, Jaime; Combe, Juan; Vargas, Gloria; Prado, William; Soudry, Ethan; Pérez, Jimena; Yudin, Tikki; Mancinelli, Andrea; Unger, Helen; Ili-Gangas, Carmen; Brebi-Mieville, Priscilla; Berg, Douglas E; Hayashi, Masamichi; Sidransky, David; Gilman, Robert H; Guerrero-Preston, Rafael.
Afiliação
  • Pirini F; Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
  • Noazin S; The Johns Hopkins University, Bloomberg School of Public Health, Department of International Health, Baltimore, MD, USA.
  • Jahuira-Arias MH; The Johns Hopkins University, School of Medicine, Otolaryngology Department, Head and Neck Cancer Research Division, Baltimore, MD, USA.
  • Rodriguez-Torres S; Universidad Peruana Cayetano Heredia, Lima, Perú.
  • Friess L; The Johns Hopkins University, School of Medicine, Otolaryngology Department, Head and Neck Cancer Research Division, Baltimore, MD, USA.
  • Michailidi C; The Johns Hopkins University, School of Medicine, Otolaryngology Department, Head and Neck Cancer Research Division, Baltimore, MD, USA.
  • Cok J; The Johns Hopkins University, School of Medicine, Otolaryngology Department, Head and Neck Cancer Research Division, Baltimore, MD, USA.
  • Combe J; Hospital Nacional Cayetano Heredia, Pathology Department, Lima, Perú.
  • Vargas G; Instituto Nacional de Enfermedades Neoplásicas, Gastroenterology Department, Lima, Perú.
  • Prado W; Hospital Nacional Arzobispo Loayza, Gastroenterology Department, Lima, Perú.
  • Soudry E; Hospital Nacional Dos de Mayo, Gastroenterology Department, Lima, Perú.
  • Pérez J; The Johns Hopkins University, School of Medicine, Otolaryngology Department, Head and Neck Cancer Research Division, Baltimore, MD, USA.
  • Yudin T; The Johns Hopkins University, School of Medicine, Otolaryngology Department, Head and Neck Cancer Research Division, Baltimore, MD, USA.
  • Mancinelli A; The Johns Hopkins University, School of Medicine, Otolaryngology Department, Head and Neck Cancer Research Division, Baltimore, MD, USA.
  • Unger H; The Johns Hopkins University, School of Medicine, Otolaryngology Department, Head and Neck Cancer Research Division, Baltimore, MD, USA.
  • Ili-Gangas C; The Johns Hopkins University, School of Medicine, Otolaryngology Department, Head and Neck Cancer Research Division, Baltimore, MD, USA.
  • Brebi-Mieville P; Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile.
  • Berg DE; Center of Excellence in Translational Medicine - Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile.
  • Hayashi M; Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile.
  • Sidransky D; Center of Excellence in Translational Medicine - Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile.
  • Gilman RH; Washington University Medical School, Department of Molecular Microbiology, St Louis, MO, USA.
  • Guerrero-Preston R; University of California San Diego, Department of Medicine, La Jolla, CA, USA.
Oncotarget ; 8(24): 38501-38516, 2017 Jun 13.
Article em En | MEDLINE | ID: mdl-28418867
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Adenocarcinoma / Biomarcadores Tumorais / Detecção Precoce de Câncer Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Adenocarcinoma / Biomarcadores Tumorais / Detecção Precoce de Câncer Idioma: En Ano de publicação: 2017 Tipo de documento: Article