TY  - JOUR
AU  - Zhang, Yan
AU  - Bewerunge-Hudler, Melanie
AU  - Schick, Matthias
AU  - Burwinkel, Barbara
AU  - Herpel, Esther
AU  - Hoffmeister, Michael
AU  - Brenner, Hermann
TI  - Blood-derived DNA methylation predictors of mortality discriminate tumor and healthy tissue in multiple organs.
JO  - Molecular oncology
VL  - 14
IS  - 9
SN  - 1878-0261
CY  - Hoboken, NJ
PB  - John Wiley & Sons, Inc.
M1  - DKFZ-2020-01226
SP  - 2111-2123
PY  - 2020
N1  - 2020 Sep;14(9):2111-2123#EA:C070#LA:C070#
AB  - Evidence has shown that certain methylation markers derived from blood can mirror corresponding methylation signatures in internal tissues. In the current study, we aimed to investigate two strong epigenetic predictors for life span, derived from blood DNA methylation data, in tissue samples of solid cancer patients. Using data from the Cancer Genome Atlas (TCGA) and the German DACHS study, we compared a mortality risk score (MRscore) and DNAmPhenoAge in paired tumor and adjacent normal tissue samples of patients with lung (N = 69), colorectal (n = 299), breast (n = 90), head/neck (n = 50), prostate (n = 50), and liver (n = 50) cancer. To explore the concordance across tissue and blood, we additionally assessed the two markers in blood samples of colorectal cancer (CRC) cases and matched controls (n = 93) in the DACHS+ study. The MRscore was significantly elevated in tumor tissues compared to normal tissues of all cancers except prostate cancer, for which an opposite pattern was observed. DNAmPhenoAge was consistently higher in all tumor tissues. The MRscore discriminated lung, colorectal, and prostate tumor tissues from normal tissues with very high accuracy [AUCs of 0.87, 0.99 (TCGA) /0.94 (DACHS), and 0.92, respectively]. DNAmPhenoAge accurately discriminated five types of tumor tissues from normal tissues (except prostate cancer), with AUCs of 0.82-0.93. The MRscore was also significantly higher in blood samples of CRC cases than in controls, with areas under the curve (AUC) of 0.74, whereas DNAmPhenoAge did not distinguish cases from controls, with AUC of 0.54. This study provides compelling evidence that blood-derived DNAm markers could reflect methylation changes in less accessible tissues. Further research should explore the potential use of these findings for cancer diagnosis and early detection.
LB  - PUB:(DE-HGF)16
C6  - pmid:32506842
DO  - DOI:10.1002/1878-0261.12738
UR  - https://inrepo02.dkfz.de/record/156919
ER  -