GPX3 hypermethylation in gastric cancer and its prognostic value in patients aged over 60

Future Oncol. 2019 Apr;15(11):1279-1289. doi: 10.2217/fon-2018-0674. Epub 2019 Mar 29.

Abstract

Aim: This study investigated the association between GPX3 methylation and gastric cancer (GC), and explored its prognostic value in patients undergoing radical gastrectomy.

Materials & methods: The methylation levels of tumor and paracancerous tissues were detected by quantitative methylation-specific PCR method.

Results: GPX3 was hypermethylated in GC (p = 4E-4), and was specific for patients with lymphatic metastasis (+), tumor invasion depth >3 cm and patients with poor differentiation. Additionally, GPX3 hypermethylation predicts a tumor recurrence in patients aged >60 (p = 0.019). Data from The Cancer Genome Atlas (TCGA) further confirmed GPX3 hypermethylation (cg21504918: -0.08 vs -0.25, p = 0.001). Additionally, TCGA showed an inverse correlation between GPX3 methylation and expression (p = 7E-18, r = -0.427). Data analysis of Gene Expression Omnibus (GEO) database showed that 5-aza-2'-deoxycytidine demethylating agent increased GPX3 expression (fold-change >2.19, p = 0.001).

Conclusion: Our results indicated GPX3 hypermethylation in GC, and predicted a shorter tumor recurrence time in patients aged >60.

Keywords: DNA methylation; GPX3; gastric cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Computational Biology / methods
  • CpG Islands
  • DNA Methylation*
  • Data Mining
  • Databases, Genetic
  • Female
  • Glutathione Peroxidase / genetics*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Promoter Regions, Genetic
  • Recurrence
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy

Substances

  • Biomarkers, Tumor
  • GPX3 protein, human
  • Glutathione Peroxidase