TY - JOUR
T1 - Colon and liver tissue damage detection using methylated SESN3 and PTK2B genes in circulating cell-free DNA in patients with acute graft-versus-host disease
AU - Waterhouse, Miguel
AU - Pennisi, Sandra
AU - Pfeifer, Dietmar
AU - Deuter, Max
AU - von Bubnoff, Nikolas
AU - Scherer, Florian
AU - Strüssmann, Tim
AU - Wehr, Claudia
AU - Duyster, Justus
AU - Bertz, Hartmut
AU - Finke, Jürgen
AU - Duque-Afonso, Jesus
N1 - Funding Information:
Funding This work was supported by a grant from Else Kröner Fresenius-Stiftung (EKFS), Nr. 2018 A56. JD-A was supported by the Berta-Ottenstein Program for Advanced Clinician Scientists, Faculty of Medicine, University of Freiburg.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Cell-free DNA (cfDNA) has been investigated in acute graft-versus-host disease (aGvHD) following allogeneic cell transplantation (HSCT). Identifying the tissue of origin of cfDNA in patients with aGvHD is relevant particularly when a biopsy is not feasible. We investigate the cfDNA tissue of origin in patients with aGvHD using methylated gene biomarkers. Patients with liver, colon, or skin aGvHD (n = 28) were analyzed. Liver- and colon-derived cfDNA was measured using a colon- (SESN3) and liver (PTK2B)-specific methylation marker with digital droplet PCR. A statistically significant difference (p < 0.001) in PTK2B and SESN3 concentration was observed between patients with colon or liver GvHD and the control group. For SESN3 and PTK2B the area under the curve in the receiver-operating characteristic (ROC) space was 0.952 (95% CI, 0.888–1 p < 0.001) and 0.971 (95% CI, 0.964–1 p < 0.001), respectively. Thresholds to differentiate aGvHD from non-aGvHD in colon were 0 (sensitivity: 0.905; specificity: 0.989) and liver 1.5 (sensitivity: 0.928; specificity: 0.910). Clinical improvement of liver or colon aGvHD resulted in PTK2B and SESN3 reduced concentration. Whereas, in those patients without improvement the PTK2B and SESN3 level remained stable or increased. The PTK2B liver-specific marker and the SESN3 colon-specific marker and their longitudinal analysis might improve aGvHD detection.
AB - Cell-free DNA (cfDNA) has been investigated in acute graft-versus-host disease (aGvHD) following allogeneic cell transplantation (HSCT). Identifying the tissue of origin of cfDNA in patients with aGvHD is relevant particularly when a biopsy is not feasible. We investigate the cfDNA tissue of origin in patients with aGvHD using methylated gene biomarkers. Patients with liver, colon, or skin aGvHD (n = 28) were analyzed. Liver- and colon-derived cfDNA was measured using a colon- (SESN3) and liver (PTK2B)-specific methylation marker with digital droplet PCR. A statistically significant difference (p < 0.001) in PTK2B and SESN3 concentration was observed between patients with colon or liver GvHD and the control group. For SESN3 and PTK2B the area under the curve in the receiver-operating characteristic (ROC) space was 0.952 (95% CI, 0.888–1 p < 0.001) and 0.971 (95% CI, 0.964–1 p < 0.001), respectively. Thresholds to differentiate aGvHD from non-aGvHD in colon were 0 (sensitivity: 0.905; specificity: 0.989) and liver 1.5 (sensitivity: 0.928; specificity: 0.910). Clinical improvement of liver or colon aGvHD resulted in PTK2B and SESN3 reduced concentration. Whereas, in those patients without improvement the PTK2B and SESN3 level remained stable or increased. The PTK2B liver-specific marker and the SESN3 colon-specific marker and their longitudinal analysis might improve aGvHD detection.
UR - http://www.scopus.com/inward/record.url?scp=85092904919&partnerID=8YFLogxK
U2 - 10.1038/s41409-020-01090-z
DO - 10.1038/s41409-020-01090-z
M3 - Journal articles
AN - SCOPUS:85092904919
SN - 0268-3369
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
ER -
