Research Paper Volume 13, Issue 12 pp 16600—16619

Development and validation of a risk prediction model and nomogram for colon adenocarcinoma based on methylation-driven genes

Liangyu Zhu1, , Hongyu Sun1, , Guo Tian2, , Juan Wang3, , Qian Zhou4, , Pu Liu1, , Xuejiao Tang1, , Xinrui Shi1, , Lei Yang1, , Guangjie Liu5, &, ,

  • 1 Department of Epidemiology and Statistics, School of Public Health, Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang 050017, P.R. China
  • 2 Department of Medical Record, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, P.R. China
  • 3 Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, P.R. China
  • 4 Department of Clinical Pharmacology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, P.R. China
  • 5 Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, P.R. China

Received: December 24, 2020       Accepted: May 13, 2021       Published: June 28, 2021
How to Cite

Copyright: © 2021 Zhu 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.


Evidence suggests that abnormal DNA methylation patterns play a crucial role in the etiology and pathogenesis of colon adenocarcinoma (COAD). In this study, we identified a total of 97 methylation-driven genes (MDGs) through a comprehensive analysis of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression analysis identified four MDGs (CBLN2, RBM47, SLCO4C1, and TMEM220) associated with overall survival (OS) in COAD patients. A risk prediction model was then developed based on these four MDGs to predict the prognosis of COAD patients. We also created a nomogram that incorporated risk scores, age, and TNM stage to promote a personalized prediction of OS in COAD patients. Compared with the traditional TNM staging system, our new nomogram was better at predicting the OS of COAD patients. In cell experiments, we confirmed that the mRNA expression levels of CLBN2 and TMEM220 were regulated by the methylation of their promoter regions. Moreover, immunohistochemistry showed that CBLN2 and TMEM220 were potential prognostic biomarkers for COAD patients. In summary, we have established a risk prediction model and nomogram that might be effectively utilized to promote the prediction of OS in COAD patients.


COAD: Colon adenocarcinoma; MDGs: Methylation-driven genes; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; OS: Overall survival; DEGs: Differentially expressed genes; DMGs: Differentially methylated genes; HR: Hazard ratio; LASSO: Least absolute shrinkage and selection operator; K-M: Kaplan-Meier; AUCs: Areas under the curves; C-index: Harrell’s concordance index; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: Gene set enrichment analysis; qPCR: Quantitative real-time PCR; 5-aza: 5-Aza-2′-deoxycytidine; MSP: Methylation specific PCR; TSGs: Tumor suppressor genes; ROC: Receiver operating characteristic; FDR: False discovery rate; TSS: transcriptional start site; TBS: Tris buffered saline; CI: Confidence interval.