Department of Urology, First Hospital of China Medical University, Shenyang, China.
Department of Urology, First Hospital of China Medical University, Shenyang, China.
Biomed Pharmacother. 2019 Oct;118:109079. doi: 10.1016/j.biopha.2019.109079. Epub 2019 Jul 24.
Accumulating research reports have indicated that long non-coding RNAs (lncRNAs) are abnormally expressed in many types of cancers. However, few lncRNA signatures for predicting cancer prognosis have been established. Our goal is to establish a lncRNA signature for predicting the prognosis of clear cell renal cell carcinoma (ccRCC).
We downloaded KIRC lncRNA FPKM (Fragments Per Kilobase of transcript per Million Fragments) standardized expression data from The Cancer Genome Atlas (TCGA) by using the TANRIC tool. We established an 11-lncRNA signature that was clearly linked to the overall survival (OS) rates in the training and test sets.
The training set was divided into the high-risk and low-risk subgroups, between which the OS was disparate (HR = 1.51, 95%CI = 1.39-1.64, P < 0.0001). The accuracy of the 11-lncRNA signature for predicting prognosis was confirmed in the test set. Further analysis revealed that the prognostic value of this signature was independent of the neoplasm grade and TNM stage. Gene set enrichment analysis (GSEA) was performed, and a summary of 4 gene sets related to canonical pathway, biological process, molecular function and cellular component was obtained. We demonstrated the biological function of these lncRNAs in ccRCC cell lines and found that LINC00488 and HOTTIP promoted tumour proliferation and inhibited apoptosis. However, LINC-PINT had the opposite effect.
The establishment of the 11-lncRNA signature indicated the underlying biochemical functional roles of the selected lncRNAs in ccRCC. Our results may provide a reliable theoretical basis for clinical evaluation of ccRCC prognosis.
越来越多的研究报告表明，长链非编码 RNA（lncRNAs）在多种癌症中表达异常。然而，很少有 lncRNA 特征可用于预测癌症预后。我们的目标是建立 lncRNA 特征，以预测透明细胞肾细胞癌（ccRCC）的预后。
我们使用 TANRIC 工具从癌症基因组图谱（TCGA）下载了 KIRC lncRNA FPKM（每百万片段的转录物每千碱基的片段）标准化表达数据。我们在训练集和测试集中建立了一个与总生存率（OS）明显相关的 11-lncRNA 特征。
训练集被分为高风险和低风险亚组，OS 存在差异（HR=1.51，95%CI=1.39-1.64，P<0.0001）。该 11-lncRNA 特征在测试集中预测预后的准确性得到了证实。进一步分析表明，该特征的预后价值独立于肿瘤分级和 TNM 分期。进行了基因集富集分析（GSEA），并获得了 4 个与经典途径、生物过程、分子功能和细胞成分相关的基因集的摘要。我们证明了这些 lncRNAs 在 ccRCC 细胞系中的生物学功能，并发现 LINC00488 和 HOTTIP 促进肿瘤增殖并抑制细胞凋亡。然而，LINC-PINT 则具有相反的作用。
该 11-lncRNA 特征的建立表明所选 lncRNAs 在 ccRCC 中潜在的生化功能作用。我们的结果可能为 ccRCC 预后的临床评估提供可靠的理论依据。
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