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000142868 1001_ $$0P:(DE-HGF)0$$aGündert, Melanie$$b0$$eFirst author
000142868 245__ $$aGenome-wide DNA methylation analysis reveals a prognostic classifier for non-metastatic colorectal cancer (ProMCol classifier).
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000142868 520__ $$aPathological 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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000142868 7001_ $$0P:(DE-He78)92820b4867c955a04f642707ecf35b40$$aEdelmann, Dominic$$b1$$udkfz
000142868 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b2$$udkfz
000142868 7001_ $$0P:(DE-He78)bbfe0ebad1e3b608bca2b49d4f86bd09$$aJansen, Lina$$b3$$udkfz
000142868 7001_ $$0P:(DE-He78)72d22b0cfac00f2fc21ceb7236804af0$$aJia, Min$$b4$$udkfz
000142868 7001_ $$0P:(DE-He78)6c2a1ea8cce3580fe2d1c1df120a92b9$$aWalter, Viola$$b5$$udkfz
000142868 7001_ $$aKnebel, Phillip$$b6
000142868 7001_ $$aHerpel, Esther$$b7
000142868 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b8$$udkfz
000142868 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b9$$udkfz
000142868 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b10$$udkfz
000142868 7001_ $$0P:(DE-He78)15b7fd2bc02d5ef47a2fe2dd0140d2bf$$aBurwinkel, Barbara$$b11$$eLast author$$udkfz
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