Research Paper Volume 11, Issue 1 pp 160—173

A four-methylated mRNA signature-based risk score system predicts survival in patients with hepatocellular carcinoma

Yu Wang1, , Zhiping Ruan1, , Sizhe Yu1, , Tao Tian1, , Xuan Liang1, , Li Jing1, , Wenyuan Li1, , Xiao Wang1, , LCL Xiang1, , F.X. Claret2, , Kejun Nan1, , Hui Guo1, ,

  • 1 Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi, PR China
  • 2 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

Received: September 16, 2018       Accepted: December 19, 2018       Published: January 10, 2019
How to Cite

Copyright: Wang 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 altered DNA methylation plays a causative role in the pathogenesis of various cancers, including hepatocellular carcinoma (HCC). Thus, methylated differently expressed genes (MDEGs) could potentially serve as biomarkers and therapeutic targets in HCC. In the present study, screening four genomics profiling datasets (GSE62232, GSE84402, GSE73003 and GSE57956) enabled us to identify a total of 148 MDEGs. A signature was then established based on the top four MDEGs (BRCA1, CAD, CDC20 and RBM8A). Taking clinical variables into consideration, we constructed a risk score system consisting of the four-MDEG signature and the patients’ clinical features, which was predictive of prognosis in HCC. The prognostic value of the HCC risk score system was confirmed using TCGA HCC samples. The scores were then used to construct a nomogram, performance of which was evaluated using Harrel’s concordance index (C-index) and a calibration curve. The signature-based nomogram for prediction of overall survival in HCC patients exhibited good performance and was superior to traditional staging systems (C-index: 0.676 vs 0.629, P< 0.05). We have thus established a novel risk score system that is predictive of prognosis and is a potentially useful guide for personalized treatment of HCC patients.


MDEG: methylated differently expressed gene; HCC: hepatocellular carcinoma; OS: overall survival; PFS: progression-free survival; HR: hazard ratio; CI: confidence interval; KM curve: Kaplan‐Meier curve.