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一种预测肝细胞癌患者生存的新型八信使核糖核酸-长链非编码核糖核酸特征的发现。

The discovery of a novel eight-mRNA-lncRNA signature predicting survival of hepatocellular carcinoma patients.

作者信息

Shi Ye-Min, Li Yan-Yan, Lin Jia-Yun, Zheng Lei, Zhu Yi-Ming, Huang Jian

机构信息

Department of Infections, Yuyao People's Hospital, Medical School of Ningbo University, Ningbo, China.

Department of Radiation Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

J Cell Biochem. 2019 May;120(5):7539-7550. doi: 10.1002/jcb.28028. Epub 2018 Nov 28.

Abstract

Increasing evidence indicates that the expressions of messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) undergo a frequent and aberrant change in carcinogenesis and cancer development. But some research was carried out on mRNA-lncRNA signatures for prediction of hepatocellular carcinoma (HCC) prognosis. We aimed to establish an mRNA-lncRNA signature to improve the ability to predict HCC patients' survival. The subjects from the cancer genome atlas (TCGA) data set were randomly divided into two parts: training data set (n = 246) and testing data set (n = 124). Using computational methods, we selected eight gene signatures (five mRNAs and three lncRNAs) to generate the risk score model, which were significantly correlated with overall survival of patients with HCC in both training and testing data set. The signature had the ability to classify the patients in training data set into a high-risk group and low-risk group with significantly different overall survival (hazard ratio = 4.157, 95% confidence interval = 2.648-6.526, P < 0.001). The prognostic value was further validated in testing data set and the entire data set. Further analysis revealed that this signature was independent of tumor stage. In addition, Gene Set Enrichment Analysis suggested that high risk score group was associated with cell proliferation and division related pathways. Finally, we developed a well-performed nomogram integrating the prognostic signature and other clinical information to predict 3- and 5-year overall survival. In conclusion, the prognostic mRNAs and lncRNAs identified in our study indicate their potential role in HCC biogenesis. The risk score model based on the mRNA-lncRNA may be an efficient classification tool to evaluate the prognosis of patients' with HCC.

摘要

越来越多的证据表明,信使核糖核酸(mRNA)和长链非编码核糖核酸(lncRNA)的表达在致癌过程和癌症发展中经常发生异常变化。但已有一些关于mRNA-lncRNA特征用于预测肝细胞癌(HCC)预后的研究。我们旨在建立一种mRNA-lncRNA特征,以提高预测HCC患者生存的能力。来自癌症基因组图谱(TCGA)数据集的受试者被随机分为两部分:训练数据集(n = 246)和测试数据集(n = 124)。我们使用计算方法选择了八个基因特征(五个mRNA和三个lncRNA)来生成风险评分模型,这些特征在训练和测试数据集中均与HCC患者的总生存期显著相关。该特征能够将训练数据集中的患者分为高风险组和低风险组,两组的总生存期有显著差异(风险比 = 4.157,95%置信区间 = 2.648 - 6.526,P < 0.001)。其预后价值在测试数据集和整个数据集中得到进一步验证。进一步分析表明,该特征独立于肿瘤分期。此外,基因集富集分析表明高风险评分组与细胞增殖和分裂相关途径有关。最后,我们开发了一个性能良好的列线图,整合了预后特征和其他临床信息,以预测3年和5年总生存期。总之,我们研究中鉴定出的预后mRNA和lncRNA表明了它们在HCC发生中的潜在作用。基于mRNA-lncRNA的风险评分模型可能是评估HCC患者预后的一种有效分类工具。

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