Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma.
Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma.
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鉴定五长非编码RNA特征以改善肝细胞癌患者的预后预测
DOI：
10.3748/wjg.v24.i30.3426
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发表时间：
2018-08-14
影响因子：
4.3
通讯作者：
Liu FF
中科院分区：
文献类型：
--
作者：
Zhao QJ;Zhang J;Xu L;Liu FF
目的构建一个高效预测肝癌预后的长链非编码RNA（lncRNA）标记。方法应用EdgeR软件包对TCGA LIHC数据集进行分析，筛选肝癌和癌旁肝组织中差异表达的lncRNAs（DELs）。采用单变量考克斯比例风险回归分析，获得训练集中与总生存期（OS）显著相关的DEL。使用逐步多变量考克斯回归模型进一步分析这些OS相关DEL。选择那些符合多变量考克斯回归模型并与总生存期独立相关的lncRNA来构建预后风险公式。然后在测试组和整个队列中验证该公式的预后价值，并将其与先前确定的两个HCC预后特征进行进一步比较。进行基因本体和京都基因百科全书和基因组途径分析以探索标签中lncRNA的潜在生物学功能。结果基于TCGA数据库中370例HCC患者的lncRNA表达谱，我们构建了与预后显著相关的5-lncRNA标签（AC015908.3，AC091057.3，TMCC 1-AS 1，DCST 1-AS 1和FOXD 2-AS 1）。在训练组和测试组中，基于5种lncRNA表达的高风险评分的HCC患者与低风险评分的患者相比，生存时间显着缩短。多因素考克斯回归分析显示5种lncRNA的预后价值与临床病理参数无关。一项涉及两个先前鉴定的HCC预后标记的比较研究表明，与其他两个标记相比，该5-lncRNA标记显示出改善的预后能力。功能富集分析表明，5个lncRNA可能参与代谢过程，纤维蛋白溶解和补体激活。结论本研究构建了一个5-lncRNA标签，可提高生存预测，并可用作HCC患者的预后生物标志物。
AIM To construct a long non-coding RNA (lncRNA) signature for predicting hepatocellular carcinoma (HCC) prognosis with high efficiency. METHODS Differentially expressed lncRNAs (DELs) between HCC specimens and peritumor liver specimens were identified using the edgeR package to analyze The Cancer Genome Atlas (TCGA) LIHC dataset. Univariate Cox proportional hazards regression was performed to obtain the DELs significantly associated with overall survival (OS) in a training set. These OS-related DELs were further analyzed using a stepwise multivariate Cox regression model. Those lncRNAs fitted in the multivariate Cox regression model and independently associated with overall survival were chosen to build a prognostic risk formula. The prognostic value of this formula was then validated in the test group and the entire cohort and further compared with two previously identified prognostic signatures for HCC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the potential biological functions of the lncRNAs in the signature. RESULTS Based on lncRNA expression profiling of 370 HCC patients from the TCGA database, we constructed a 5-lncRNA signature (AC015908.3, AC091057.3, TMCC1-AS1, DCST1-AS1 and FOXD2-AS1) that was significantly associated with prognosis. HCC patients with high-risk scores based on the expression of the 5 lncRNAs had significantly shorter survival times compared to patients with low-risk scores in both the training and test groups. Multivariate Cox regression analysis demonstrated that the prognostic value of the 5 lncRNAs was independent of clinicopathological parameters. A comparison study involving two previously identified prognostic signatures for HCC demonstrated that this 5-lncRNA signature showed improved prognostic power compared with the other two signatures. Functional enrichment analysis indicated that the 5 lncRNAs were potentially involved in metabolic processes, fibrinolysis and complement activation. CONCLUSION Our present study constructed a 5-lncRNA signature that improves survival prediction and can be used as a prognostic biomarker for HCC patients.
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