Identification and validation of a prognostic four-genes signature for hepatocellular carcinoma: integrated ceRNA network analysis
Identification and validation of a prognostic four-genes signature for hepatocellular carcinoma: integrated ceRNA network analysis
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肝细胞癌预后四基因特征的鉴定和验证：集成 ceRNA 网络分析
DOI：
10.1007/s12072-019-09962-3
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发表时间：
2019-09-01
影响因子：
6.6
通讯作者：
Xiao, Zhiyu
中科院分区：
文献类型：
--
作者：
Yan, Yongcong;Lu, Yingjuan;Xiao, Zhiyu
背景：肝细胞癌是世界范围内侵袭性最强的恶性肿瘤之一，远期预后较差。整体转录组功能缺失与肝细胞癌的发生发展密切相关，但缺乏系统的研究和验证。我们构建了一个交互的、可视化的竞争内源RNA网络。用最小绝对收缩和选择算子算法建立预测特征。结果：在训练集中，我们识别了一个四基因标记(PBK、CBX2、CLSPN和CPEB3)，并有效地预测了总生存期。高分组患者的生存时间比低分组差(p=0.0004)，高分组患者死亡的可能性也更大(HR为2.444，p<；0.001)。结果在内部验证集(p=0.0057)和两个外部验证队列(HR 2.467和2.6%)中进行了验证。1、2、3年AUC分别为0.716、0.726、0.714。结论：我们成功构建了一个更广泛的肝细胞癌CENA网络，并确定了一个基于4个基因的标记，从而能够预测肝细胞癌患者的总体生存。
Background:Hepatocellular carcinoma (HCC) is one of the most aggressive malignant tumors, with a poor long-term prognosis worldwide. The functional deregulations of global transcriptome were associated with the genesis and development of HCC, but lacks systematic research and validation.Methods:A total of 519 postoperative HCC patients were included. We built an interactive and visual competing endogenous RNA network. The prognostic signature was established with the least absolute shrinkage and selection operator algorithm. Multivariate Cox regression analysis was used to screen for independent prognostic factors for HCC overall survival.Results:In the training set, we identified a four-gene signature (PBK, CBX2, CLSPN, and CPEB3) and effectively predicted the overall survival. The survival times of patients in the high-score group were worse than those in the low-score group (p = 0.0004), and death was also more likely in the high-score group (HR 2.444, p < 0.001). The results were validated in internal validation set (p = 0.0057) and two external validation cohorts (HR 2.467 and 2.6). The signature (AUCs of 1, 2, 3 years were 0.716, 0.726, 0.714, respectively) showed high prognostic accuracy in the complete TCGA cohort.Conclusions:In conclusion, we successfully built a more extensive ceRNA network for HCC and then identified a four-gene-based signature, enabling prediction of the overall survival of patients with HCC.