Journal Article

DKFZ-2019-00498

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genome-wide DNA methylation analysis reveals a prognostic classifier for non-metastatic colorectal cancer (ProMCol classifier).

Gündert, M. (First author)DKFZ* ; Edelmann, D.DKFZ* ; Benner, A.DKFZ* ; Jansen, L.DKFZ* ; Jia, M.DKFZ* ; Walter, V.DKFZ* ; Knebel, P. ; Herpel, E. ; Chang-Claude, J.DKFZ* ; Hoffmeister, M.DKFZ* ; Brenner, H.DKFZ* ; Burwinkel, B. (Last author)DKFZ*

2019
BMJ Publishing Group London

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Please use a persistent id in citations: doi:10.1136/gutjnl-2017-314711

Abstract: Pathological staging used for the prediction of patient survival in colorectal cancer (CRC) provides only limited information.Here, a genome-wide study of DNA methylation was conducted for two cohorts of patients with non-metastatic CRC (screening cohort (n=572) and validation cohort (n=274)). A variable screening for prognostic CpG sites was performed in the screening cohort using marginal testing based on a Cox model and subsequent adjustment of the p-values via independent hypothesis weighting using the methylation difference between 34 pairs of tumour and normal mucosa tissue as auxiliary covariate. From the 1000 CpG sites with the smallest adjusted p-value, 20 CpG sites with the smallest Brier score for overall survival (OS) were selected. Applying principal component analysis, we derived a prognostic methylation-based classifier for patients with non-metastatic CRC (ProMCol classifier).This classifier was associated with OS in the screening (HR 0.51, 95% CI 0.41 to 0.63, p=6.2E-10) and the validation cohort (HR 0.61, 95% CI 0.45 to 0.82, p=0.001). The independent validation of the ProMCol classifier revealed a reduction of the prediction error for 3-year OS from 0.127, calculated only with standard clinical variables, to 0.120 combining the clinical variables with the classifier and for 4-year OS from 0.153 to 0.140. All results were confirmed for disease-specific survival.The ProMCol classifier could improve the prognostic accuracy for patients with non-metastatic CRC.

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Contributing Institute(s):

1. Molekulare Epidemiologie (C080)
2. C060 Biostatistik (C060)
3. C070 Klinische Epidemiologie und Alternf. (C070)
4. C020 Epidemiologie von Krebs (C020)
5. Präventive Onkologie (C120)
6. DKTK Heidelberg (L101)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2019

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Database coverage:
; Allianz-Lizenz ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 15 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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