4.5 Article

Methylation of immune-regulatory cytokine genes and pancreatic cancer outcomes

Journal

EPIGENOMICS
Volume 12, Issue 15, Pages 1273-1285

Publisher

FUTURE MEDICINE LTD
DOI: 10.2217/epi-2019-0335

Keywords

cytokines; epigenetics; immune system; methylation; pancreatic cancer; progression; survival

Funding

  1. National Cancer Institute of the National Institutes of Health [K07CA225856, T32CA009142]
  2. NCI/NIH [T32CA009142, T32CA229110]

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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,TGF beta 1,TGF beta 2,TGF beta 3andTNF. We used Cox regression to evaluate the associations between methylation and overall survival, disease-specific survival and disease progression (alpha = 0.05).Results:Poorer survival was associated with increased methylation in fifteen CpG probes inTGF beta 1,TGF beta 2,TGF beta 3andTNF. We also detected improved outcomes for three loci inIL10,IL8andIL6.Conclusion:Epigenetic regulation of cytokine-related gene expression may be associated with pancreatic cancer outcomes.

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