Demethylation of the TSDR is a marker of squamous cell carcinoma in transplant recipients

Am J Transplant. 2014 Nov;14(11):2617-22. doi: 10.1111/ajt.12899. Epub 2014 Sep 23.

Abstract

Malignancy is an important cause of death in transplant recipients. Cutaneous squamous cell carcinoma (cSCC) causes significant morbidity and mortality as 30% of transplant recipients will develop cSCC within 10 years of transplantation. Previously we have shown that high numbers of regulatory T cells (Tregs) are associated with the development of cSCC in kidney transplant recipients (KTRs). Demethylation analysis of the Treg-specific demethylated region (TSDR) provides a more accurate association with cSCC risk after transplantation. Age, gender and duration of immunosuppression matched KTRs with (n=32) and without (n=27) cSCC, were re-analyzed for putative clinical and immunological markers of cancer risk. The proportion of FOXP3+ CD4+ cells was higher in the population with a previous SCC. Major T cell subsets remained stable over time; although B cell, CD8 and CD4 subpopulations demonstrated age-related changes. TSDR methylation analysis allowed clarification of Treg numbers, enhancing the association of high Treg levels in KTRs with cSCC compared to the cSCC-free cohort. These data validate and expand on previous findings in long-term KTRs, and show that immune markers remain stable over time. TSDR demethylation analysis provides a more accurate biomarker of cancer posttransplantation.

Keywords: Basic (laboratory) research/science; biomarker; cancer/malignancy/neoplasia: skin; flow cytometry; immune regulation; immunobiology; kidney transplantation/nephrology; monitoring: immune; nonmelanoma; organ transplantation in general; translational research/science.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Carcinoma, Squamous Cell / blood*
  • DNA Methylation*
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Male
  • Middle Aged
  • Transplantation / adverse effects*

Substances

  • Biomarkers, Tumor
  • Immunosuppressive Agents