Disrupted regulation of serpinB9 in circulating T cells is associated with an increased risk for post-transplant skin cancer.
Clin Exp Immunol
; 197(3): 341-351, 2019 09.
Article
in En
| MEDLINE
| ID: mdl-31059128
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin Neoplasms
/
Carcinoma, Squamous Cell
/
T-Lymphocytes
/
Down-Regulation
/
Serpins
/
Kidney Transplantation
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Clin Exp Immunol
Year:
2019
Document type:
Article