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

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

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

https://doi.org/10.18632/aging.203179

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.

Abstract

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.