Disrupted regulation of serpinB9 in circulating T cells is associated with an increased risk for post-transplant skin cancer
Cutaneous squamous cell carcinoma (cSCC) is a serious complication after organ transplantation and patients benefit from an early risk assessment. We hypothesized that functional differences in circulating T cells may represent risk factors for post-transplant cSCC development. Here, we analysed genome-wide DNA methylation of circulating T cells of kidney transplant recipients before the clinical onset of cSCC, to identify differences associated with post-transplant cSCC development. This analysis identified higher DNA methylation of SERPINB9, which is an intracellular inhibitor of granzyme B, a protein that induces apoptosis in target cells. High DNA methylation of SERPINB9 in circulating T cells was confirmed in a second patient cohort during recurrent cSCC, indicating that high SERPINB9 methylation represents a persistent risk factor for cSCC development. At the functional level, the inverse correlation between DNA methylation and messenger RNA expression present in non-cSCC patients was absent in the cSCC patients. Also, a significant difference in serpinB9 protein expression between cSCC patients and non-cSCC patients was observed. It was concluded that disturbed regulation of serpinB9 in circulating T cells represents a novel risk factor for post-transplant cSCC in kidney transplant recipients.
|Keywords||cutaneous squamous cell carcinoma, DNA methylation, epigenetics, kidney transplantation, PI-9|
|Persistent URL||dx.doi.org/10.1111/cei.13309, hdl.handle.net/1765/119007|
|Journal||Clinical and Experimental Immunology|
Peters, F.S, Peeters, A.M.A. (A. M.A.), van den Bosch, T.P.P. (T. P.P.), Mooyaart, A.L, van de Wetering, J, Betjes, M.G.H, … Boer, K. (2019). Disrupted regulation of serpinB9 in circulating T cells is associated with an increased risk for post-transplant skin cancer. Clinical and Experimental Immunology, 197(3), 341–351. doi:10.1111/cei.13309