eprintid: 26894
rev_number: 13
eprint_status: archive
userid: 1589
dir: disk0/00/02/68/94
datestamp: 2019-08-20 12:21:07
lastmod: 2019-09-21 11:41:15
status_changed: 2019-08-20 12:21:07
type: article
metadata_visibility: show
creators_name: Jia, Min
creators_name: Zhang, Yan
creators_name: Jansen, Lina
creators_name: Walter, Viola
creators_name: Edelmann, Dominic
creators_name: Gündert, Melanie
creators_name: Tagscherer, Katrin E.
creators_name: Roth, Wilfried
creators_name: Bewerunge-Hudler, Melanie
creators_name: Herpel, Esther
creators_name: Kloor, Matthias
creators_name: Ulrich, Alexis
creators_name: Burwinkel, Barbara
creators_name: Bläker, Hendrik
creators_name: Chang-Claude, Jenny
creators_name: Brenner, Hermann
creators_name: Hoffmeister, Michael
title: A prognostic CpG score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival
subjects: 610
divisions: 850300
divisions: 912000
keywords: Colorectal cancer, Survival, DNA methylation, CpG site, Prognosis
abstract: Background: Results of previous studies on the association of the CpG island methylator phenotype (CIMP) with colorectal cancer (CRC) prognosis were inconsistent and mostly based on different CIMP definitions. The current study aimed to comprehensively investigate the associations between DNA methylation on genes previously used to define CIMP status with CRC survival.

Results: Patients with CRC followed up for a median of 5.2 years were divided into a study cohort (n = 568) and a validation cohort (n = 308). DNA methylation was measured in tumor tissue using the Illumina Infinium HumanMethylation450 BeadChip and restricted to 43 genes used to define CIMP status in previous studies. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) of survival after CRC, including adjustment for tumor stage, microsatellite instability, and BRAF mutation status. In the study cohort, ten CpG sites were identified to be associated with CRC survival. Seven of these ten CpG sites were also associated with CRC survival in the validation cohort and were used to construct a prognostic score. CRC patients with a prognostic score of the lowest methylation level showed poorer disease-specific survival compared with patients with the highest methylation level in both the study cohort and the validation cohort (HR = 3.11 and 95% CI = 1.97–4.91, and HR = 3.06 and 95% CI = 1.71–5.45, respectively).

Conclusions: A CpG panel consisting of seven CpG sites was found to be strongly associated with CRC survival, independent from important clinical factors and mutations associated with CIMP. Further studies are required to confirm these findings.
date: 2019
publisher: BioMed Central ; Springer
id_scheme: DOI
ppn_swb: 1677085401
own_urn: urn:nbn:de:bsz:16-heidok-268946
language: eng
bibsort: JIAMINAPROGNOSTI2019
full_text_status: public
publication: Clinical Epigenetics
volume: 11
number: 109
place_of_pub: London ; Berlin, Heidelberg
pagerange: 1-11
issn: 1868-7083
citation:   Jia, Min ; Zhang, Yan ; Jansen, Lina ; Walter, Viola ; Edelmann, Dominic ; Gündert, Melanie ; Tagscherer, Katrin E. ; Roth, Wilfried ; Bewerunge-Hudler, Melanie ; Herpel, Esther ; Kloor, Matthias ; Ulrich, Alexis ; Burwinkel, Barbara ; Bläker, Hendrik ; Chang-Claude, Jenny ; Brenner, Hermann ; Hoffmeister, Michael  (2019) A prognostic CpG score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival.  Clinical Epigenetics, 11 (109).  pp. 1-11.  ISSN 1868-7083     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/26894/1/13148_2019_Article_703.pdf