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

Francesca Pirini, Sassan Noazin, Martha H. Jahuira-Arias, Sebastian Rodriguez-Torres, Leah Friess, Christina Michailidi, Jaime Cok, Juan Combe, Gloria Vargas, William Prado, Ethan Soudry, Jimena Pérez, Tikki Yudin, Andrea Mancinelli, Helen Unger, Carmen Ili-Gangas, Priscilla Brebi-Mieville, Douglas E. Berg, Masamichi Hayashi, David SidranskyRobert H. Gilman, Rafael Guerrero-Preston

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)38501-38516
Number of pages16
JournalOncotarget
Volume8
Issue number24
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • ELMO1
  • Epigenome-wide DNA methylation analysis
  • Global DNA methylation index
  • IRF4
  • Translational epigenomics

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies'. Together they form a unique fingerprint.

  • Cite this

    Pirini, F., Noazin, S., Jahuira-Arias, M. H., Rodriguez-Torres, S., Friess, L., Michailidi, C., Cok, J., Combe, J., Vargas, G., Prado, W., Soudry, E., Pérez, J., Yudin, T., Mancinelli, A., Unger, H., Ili-Gangas, C., Brebi-Mieville, P., Berg, D. E., Hayashi, M., ... Guerrero-Preston, R. (2017). Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies. Oncotarget, 8(24), 38501-38516. https://doi.org/10.18632/oncotarget.16258