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

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.