A novel CpG-methylation-based nomogram predicts survival in colorectal cancer. Issue 11 (1st November 2020)

• Record Type: Journal Article
• Authors: Wang, Xiaokang; Wang, Danwen; Liu, Jinfeng; Feng, Maohui; Wu, Xiongzhi
• Is Part Of: Epigenetics. Volume 15:Issue 11(2020)
• Page Start: 1213
• Page End: 1227
• Publication Date: 2020-11-01
• Subjects: DNA methylation -- colorectal cancer -- nomogram -- prognosis -- survival analysis; Epigenesis -- Periodicals; Epigenetica; 572.86505
• DOI: 10.1080/15592294.2020.1762368
• Languages: English
• ISSNs: 1559-2294

Abstract

ABSTRACT: Aberrant DNA methylation is significantly associated with the prognosis of patients with colorectal cancer (CRC). Therefore, the aim of this study was to develop a CpG-methylation-based nomogram for prognostic prediction in CRC. First, 378 CRC patients with methylation data from The Cancer Genome Atlas were randomly divided into training cohort (n = 249) and test cohort (n = 129). A multistep screening strategy was performed to identify six CpG sites that were significantly associated with overall survival in the training cohort. Then, Cox regression modelling was performed to construct a prognostic signature based on the candidate CpG sites. The six-CpG signature successfully separated patients into high-risk and low-risk groups in both training and test cohorts, and its performance was superior to that of previously published methylation markers ( P < 0.05). Furthermore, we established a prognostic nomogram incorporating this signature, TNM stage, and age. The nomogram exhibited better prediction for overall survival in comparison with the three independent prognostic factors in the training cohort (C-index: 0.798 vs 0.620 to 0.737; P < 0.001). In the test cohort, the performance of nomogram was also superior to that of the three independent prognostic factors (C-index: 0.715 vs 0.590 to 0.665; P < 0.05). Meanwhile, the calibration curves for survival probability showed good agreement between prediction by nomogram and actual observation in both training and test cohorts. Together, the present study provides a novel CpG-methylation-based nomogram as a promising predictor for overall survival of CRC patients, which may help improve decision-making regarding the personalized treatments of patients with CRC.