An Integrated Three-Long Non-coding RNA Signature Predicts Prognosis in Colorectal Cancer Patients
An Integrated Three-Long Non-coding RNA Signature Predicts Prognosis in Colorectal Cancer Patients
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整合的三长非编码 RNA 特征可预测结直肠癌患者的预后
DOI：
10.3389/fonc.2019.01269
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发表时间：
2019-11-22
影响因子：
4.7
通讯作者：
Huang, Zhaohui
中科院分区：
文献类型：
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作者：
Liu, Yuhang;Liu, Bingxin;Huang, Zhaohui
结直肠癌(CRC)是世界范围内最常见的癌症之一，其发病率和死亡率逐渐上升。在这里，我们的目标是识别和访问与结直肠癌总生存期(OS)相关的预后长非编码RNA(LncRNAs)。首先，从癌症基因组图谱(TCGA)数据库中获取RNA表达谱，并以439例结直肠癌患者作为训练集。用单变量Cox分析和最小绝对收缩和选择算子分析(LASSO)来识别预后的LncRNA。采用多因素Cox回归分析，建立包含AP003555.2、AP006284.1和LINC01602三个LncRNAs的预后危险公式。低风险组的OS优于高风险组(P<；0.0001)，3年和5年OS的受试者操作特征曲线(AUC)下面积分别为0.712和0.674。然后，我们在江南大学附属医院收集的临床验证集上对签名进行了评估。与低危组相比，高危组患者的OS明显更差(P=0.0057)。3年和5年OS的AUC分别为0.701和0.694。最后，我们构建了一个LncRNA-microRNA(MiRNA)-Messenger RNA(MRNA)竞争的内源RNA(Cerna)网络，以探索三个差异表达的LncRNAs(DElncRNAs)的潜在功能。京都基因和基因组百科全书(KEGG)的途径分析表明，这些DElncRNAs参与了几条与癌症相关的途径。综上所述，我们的数据提供了证据，证明3-lncRNA签名可以作为预测CRC预后的独立生物标志物。这项研究还表明，这三个LncRNAs可能参与了结直肠癌的进展。
Colorectal cancer (CRC) is one of the most common cancers worldwide, whose morbidity and mortality gradually increased. Here, we aimed to identify and access prognostic long non-coding RNAs (lncRNAs) associated with overall survival (OS) in CRC. Firstly, RNA expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and 439 CRC patients were enrolled as a training set. Univariate Cox analysis and the least absolute shrinkage and selection operator analysis (LASSO) were performed to identify the prognostic lncRNAs. Multivariable Cox regression analysis was used to establish a prognostic risk formula including three lncRNAs (AP003555.2, AP006284.1, and LINC01602). The low-risk group had a better OS than the high-risk group (P < 0.0001), and the areas under the receiver operating characteristic curve (AUCs) of 3- and 5-year OS were 0.712 and 0.674, respectively. Then, we evaluated the signature in a clinical validation set which were collected from the Affiliated Hospital of Jiangnan University. Compared with the low-risk group, patients' OS were found to be significantly worse in the high-risk group (P = 0.0057). The AUCs of 3- and 5-year OS were 0.701 and 0.694, respectively. Finally, we constructed an lncRNA-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) network to explore the potential function of three differentially expressed lncRNAs (DElncRNAs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these DElncRNAs were involved with several cancer-related pathways. In summary, our data provide evidence that the three-lncRNA signature could serve as an independent biomarker to predict prognosis in CRC. This study will also suggest that these three lncRNAs potentially participate in the progression of CRC.