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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| Hauptverfasser: | , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2019
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| In: |
Gut
Year: 2019, Jahrgang: 68, Pages: 101-110 |
| ISSN: | 1468-3288 |
| DOI: | 10.1136/gutjnl-2017-314711 |
| Online-Zugang: | 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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| Verfasserangaben: | 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 |
MARC
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| 245 | 1 | 0 | |a Genome-wide DNA methylation analysis reveals a prognostic classifier for non-metastatic colorectal cancer (ProMCol classifier) |c 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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| 500 | |a Published online first: 3 November 2017 | ||
| 520 | |a 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. | ||
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