A four-methylated mRNA signature-based risk score system predicts survival in patients with hepatocellular carcinoma
A four-methylated mRNA signature-based risk score system predicts survival in patients with hepatocellular carcinoma
复制标题
基于四甲基化 mRNA 特征的风险评分系统可预测肝细胞癌患者的生存
DOI：
10.18632/aging.101738
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发表时间：
2019-01-15
期刊：
影响因子：
5.2
通讯作者：
Guo, Hui
中科院分区：
文献类型：
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作者：
Wang, Yu;Ruan, Zhiping;Guo, Hui
有证据表明，改变的DNA甲基化在包括肝细胞癌（HCC）在内的各种癌症的发病机制中起着致病作用。因此，甲基化差异表达基因（MDEG）可能成为HCC的生物标志物和治疗靶点。在本研究中，筛选四个基因组学分析数据集（GSE 62232，GSE 84402，GSE 73003和GSE 57956）使我们能够识别出总共148个MDEG。然后基于前四个MDEG（BRCA 1、CAD、CDC 20和RBM8A）建立特征。考虑到临床变量，我们构建了一个风险评分系统，包括四个MDEG签名和患者的临床特征，这是预测肝癌的预后。使用TCGA HCC样本证实了HCC风险评分系统的预后价值。然后使用评分构建诺模图，使用Harrel一致性指数（C指数）和校准曲线评估其性能。基于体征的诺模图预测肝癌患者的总生存率表现出良好的性能，并优于传统分期系统（C指数：0.676 vs 0.629，P< 0.05）的上级。因此，我们建立了一个新的风险评分系统，预测预后，是一个潜在的有用的指导肝癌患者的个性化治疗。
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.