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@ARTICLE{Zhang:156919,
author = {Y. Zhang and M. Bewerunge-Hudler$^*$ and M. Schick$^*$ and
B. Burwinkel$^*$ and E. Herpel and M. Hoffmeister$^*$ and H.
Brenner$^*$},
title = {{B}lood-derived {DNA} methylation predictors of mortality
discriminate tumor and healthy tissue in multiple organs.},
journal = {Molecular oncology},
volume = {14},
number = {9},
issn = {1878-0261},
address = {Hoboken, NJ},
publisher = {John Wiley $\&$ Sons, Inc.},
reportid = {DKFZ-2020-01226},
pages = {2111-2123},
year = {2020},
note = {2020 Sep;14(9):2111-2123#EA:C070#LA:C070#},
abstract = {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.},
cin = {C070 / HD01 / W110 / C080 / C120},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)W110-20160331 / I:(DE-He78)C080-20160331 /
I:(DE-He78)C120-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32506842},
doi = {10.1002/1878-0261.12738},
url = {https://inrepo02.dkfz.de/record/156919},
}