Research Paper Volume 12, Issue 22 pp 22814—22839

Analysis of DNA methylation-driven genes for predicting the prognosis of patients with colorectal cancer

Boshi Fu1,2, *, , Cheng Du1,2, *, , Zhikun Wu1,2, , Mingwei Li1,2, , Yi Zhao1,2, , Xinli Liu3, , Huizhe Wu1,2, , Minjie Wei1,2, ,

  • 1 Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China
  • 2 Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang 110122, P. R. China
  • 3 Department of Digestive Oncology, Cancer Hospital of China Medical University, Shenyang 110042, Liaoning Province, P. R. China
* Equal contribution

Received: May 26, 2020       Accepted: August 8, 2020       Published: November 16, 2020
How to Cite

Copyright: © 2020 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Aberrant promoter methylation and ensuing abnormal gene expression are important epigenetic mechanisms that contribute to colorectal oncogenesis. Yet, the prognostic significance of such methylation-driven genes in colorectal cancer (CRC) remains obscure. Herein, a total of 181 genes were identified as the methylation-driven molecular features of CRC by integrated analysis of the expression profiles and the matched DNA methylation data from The Cancer Genome Atlas (TCGA) database. Among them, a five-gene signature (POU4F1, NOVA1, MAGEA1, SLCO4C1, and IZUMO2) was developed as a risk assessment model for predicting the clinical outcomes in CRC. The Kaplan–Meier analysis and Harrell’s C index demonstrated that the risk assessment model significantly distinguished the patients in high or low-risk groups (p-value < 0.0001 log-rank test, HR: 2.034, 95% CI: 1.419-2.916, C index: 0.655). The sensitivity and specificity were validated by the receiver operating characteristic (ROC) analysis. Furthermore, different pharmaceutical treatment responses were observed between the high-risk and low-risk groups. Indeed, the methylation-driven gene signature could act as an independent prognostic evaluation biomarker for assessing the OS of CRC patients and guiding the pharmaceutical treatment. Compared with known biomarkers, the methylation-driven gene signature could reveal cross-omics molecular features for improving clinical stratification and prognosis.


CRC: colorectal cancer; OS: Overall survival; TCGA: The Cancer Genome Atlas; DEGs: differential expression genes; CI: Confidence interval; HR: hazard ratio; ROC: Receiver operating characteristic; AUC: Area under the ROC curve.