Methylation of Immune-Regulatory Cytokine Genes and Pancreatic Cancer Outcomes

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

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2144/btn-2019-0335

Disclaimer

The results of this study are based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. This work used computational and storage services associated with the Hoffman2 Shared Cluster provided by UCLA Institute for Digital Research and Education’s Research Technology Group.

Financial & competing interests disclosure

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health (K07CA225856 to AM Binder, T32CA009142 to ZF Zhang). BZ Huang is supported by T32 Training Grants from the NCI/NIH (T32CA009142, T32CA229110; https://www.cancer.gov/). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health (K07CA225856 to AM Binder, T32CA009142 to ZF Zhang). BZ Huang is supported by T32 Training Grants from the NCI/NIH (T32CA009142, T32CA229110; https://www.cancer.gov/). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.