Methylation-mediated gene silencing as biomarkers of gastric cancer: a review

World J Gastroenterol. 2014 Sep 14;20(34):11991-2006. doi: 10.3748/wjg.v20.i34.11991.

Abstract

Despite a decline in the overall incidence of gastric cancer (GC), the disease remains the second most common cause of cancer-related death worldwide and is thus a significant global health problem. The best means of improving the survival of GC patients is to screen for and treat early lesions. However, GC is often diagnosed at an advanced stage and is associated with a poor prognosis. Current diagnostic and therapeutic strategies have not been successful in decreasing the global burden of the disease; therefore, the identification of reliable biomarkers for an early diagnosis, predictive markers of recurrence and survival and markers of drug sensitivity and/or resistance is urgently needed. The initiation and progression of GC depends not only on genetic alterations but also epigenetic changes, such as DNA methylation and histone modification. Aberrant DNA methylation is the most well-defined epigenetic change in human cancers and is associated with inappropriate gene silencing. Therefore, an increasing number of genes methylated at the promoter region have been targeted as possible biomarkers for different purposes, including early detection, classification, the assessment of the tumor prognosis, the development of therapeutic strategies and patient follow-up. This review article summarizes the current understanding and recent evidence regarding DNA methylation markers in GC with a focus on the clinical potential of these markers.

Keywords: Biomarker; Drug sensitivity; Early detection; Gastric cancer; Methylation.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • DNA Methylation*
  • Drug Resistance, Neoplasm / genetics
  • Early Detection of Cancer
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Humans
  • Patient Selection
  • Pharmacogenetics
  • Phenotype
  • Precision Medicine
  • Predictive Value of Tests
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor