In:
Gut, BMJ, Vol. 68, No. 1 ( 2019-01), p. 101-110
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0017-5749
,
1468-3288
DOI:
10.1136/gutjnl-2017-314711
Language:
English
Publisher:
BMJ
Publication Date:
2019
detail.hit.zdb_id:
1492637-4
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