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

机译:基于四甲基化mRNA签名的风险评分系统可预测肝细胞癌患者的生存率

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摘要

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 (, , and ) 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.
机译:有证据表明,DNA甲基化改变在包括肝细胞癌(HCC)在内的各种癌症的发病机理中起着致病作用。因此,甲基化的差异表达基因(MDEGs)可能作为肝癌的生物标志物和治疗靶标。在本研究中,筛选四个基因组图谱数据集(,和)使我们能够鉴定总共148个MDEG。然后根据前四个MDEG(BRCA1,CAD,CDC20和RBM8A)建立签名。考虑到临床变量,我们构建了由四个MDEG签名和患者临床特征组成的风险评分系统,该系统可预测HCC的预后。使用TCGA HCC样本确认了HCC风险评分系统的预后价值。然后将这些分数用于构建列线图,并使用Harrel的一致性指数(C-index)和校准曲线评估其性能。基于签名的列线图可预测HCC患者的总体生存情况,表现良好,优于传统的分期系统(C指数:0.676 vs 0.629,P <0.05)。因此,我们已经建立了一种新颖的风险评分系统,该系统可预测预后,并且对于HCC患者的个性化治疗可能是有用的指南。

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