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

• Verfasst von: Gündert, Melanie [VerfasserIn]
• Verfasst von: Edelmann, Dominic [VerfasserIn]
• Verfasst von: Benner, Axel [VerfasserIn]
• Verfasst von: Jansen, Lina [VerfasserIn]
• Verfasst von: Walter, Viola [VerfasserIn]
• Verfasst von: Knebel, Phillip [VerfasserIn]
• Verfasst von: Herpel, Esther [VerfasserIn]
• Verfasst von: Chang-Claude, Jenny [VerfasserIn]
• Verfasst von: Hoffmeister, Michael [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Verfasst von: Burwinkel, Barbara [VerfasserIn]
• Titel: Genome-wide DNA methylation analysis reveals a prognostic classifier for non-metastatic colorectal cancer (ProMCol classifier)
• Verf.angabe: 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
• Jahr: 2019
• Jahr des Originals: 2017
• Umfang: 10 S.
• Teil: volume:68
• Teil: year:2019
• Teil: pages:101-110
• Teil: extent:10
• Fussnoten: Gesehen am 11.02.2019 ; Published online first: 3 November 2017
• Titel Quelle: Enthalten in: Gut
• Ort Quelle: London : BMJ Publishing Group, 1960
• Jahr Quelle: 2019
• Band/Heft Quelle: 68(2019), Seite 101-110
• ISSN Quelle: 1468-3288
• DOI: doi:10.1136/gutjnl-2017-314711
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cancer epidemiology
• Sach-SW: colorectal cancer
• Sach-SW: methylation
• K10plus-PPN: 1578329264

Abstract

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.