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Genome-wide DNA methylation analysis reveals a prognostic classifier for non-metastatic colorectal cancer (ProMCol classifier)

OBJECTIVE: Pathological staging used for the prediction of patient survival in colorectal cancer (CRC) provides only limited information. DESIGN: 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 co...

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Main Authors: Gündert, Melanie (Author) , Edelmann, Dominic (Author) , Benner, Axel (Author) , Jansen, Lina (Author) , Walter, Viola (Author) , Knebel, Phillip (Author) , Herpel, Esther (Author) , Chang-Claude, Jenny (Author) , Hoffmeister, Michael (Author) , Brenner, Hermann (Author) , Burwinkel, Barbara (Author)
Format: Article (Journal)
Language:English
Published: 2019
In: Gut
Year: 2019, Volume: 68, Pages: 101-110
ISSN:1468-3288
DOI:10.1136/gutjnl-2017-314711
Online Access:Verlag, Pay-per-use, Volltext: https://gut.bmj.com/content/early/2017/11/03/gutjnl-2017-314711
Resolving-System, Pay-per-use, Volltext: http://dx.doi.org/10.1136/gutjnl-2017-314711
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Author Notes:Melanie Gündert, Dominic Edelmann, Axel Benner, Lina Jansen, Min Jia, Viola Walter, Phillip Knebel, Esther Herpel, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Barbara Burwinkel
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Summary:OBJECTIVE: Pathological staging used for the prediction of patient survival in colorectal cancer (CRC) provides only limited information. DESIGN: 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). RESULTS: 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. CONCLUSION: The ProMCol classifier could improve the prognostic accuracy for patients with non-metastatic CRC.
Item Description:Gesehen am 11.02.2019
Published online first: 3 November 2017
Physical Description:Online Resource
ISSN:1468-3288
DOI:10.1136/gutjnl-2017-314711

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