Methylation of immune-regulatory cytokine genes and pancreatic cancer outcomes

Epigenomics. 2020 Aug;12(15):1273-1285. doi: 10.2217/epi-2019-0335. Epub 2020 Sep 1.

Abstract

Aim: Given the immunosuppressive nature of pancreatic cancer, we investigated the relationship between epigenetic modification of immune-regulatory cytokine genes and pancreatic cancer outcomes. Materials & methods: We evaluated DNA methylation of 184 pancreatic tumor samples from The Cancer Genome Atlas for 111 CpG loci in seven cytokine genes: IL10, IL6, IL8, TGFβ1, TGFβ2, TGFβ3 and TNF. We used Cox regression to evaluate the associations between methylation and overall survival, disease-specific survival and disease progression (α = 0.05). Results: Poorer survival was associated with increased methylation in fifteen CpG probes in TGFβ1, TGFβ2, TGFβ3 and TNF. We also detected improved outcomes for three loci in IL10, IL8 and IL6. Conclusion: Epigenetic regulation of cytokine-related gene expression may be associated with pancreatic cancer outcomes.

Keywords: cytokines; epigenetics; immune system; methylation; pancreatic cancer; progression; survival.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • CpG Islands
  • Cytokines / genetics*
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics*
  • Retrospective Studies
  • Survival Analysis

Substances

  • Cytokines