Department of Clinical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People's Hospital, 13 Dancun Road, Nanning, 530031, Guangxi Zhuang Autonomous Region, People's Republic of China.
Department of Pathology, The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People's Hospital, 13 Dancun Road, Nanning, 530031, Guangxi Zhuang Autonomous Region, People's Republic of China.
J Transl Med. 2019 Aug 23;17(1):281. doi: 10.1186/s12967-019-2032-y.
The scientific understanding of long non-coding RNAs (lncRNAs) has improved in recent decades. Nevertheless, there has been little research into the role that lncRNAs play in clear cell renal cell carcinoma (ccRCC). More lncRNAs are assumed to influence the progression of ccRCC via their own molecular mechanisms.
This study investigated the prognostic significance of differentially expressed lncRNAs by mining high-throughput lncRNA-sequencing data from The Cancer Genome Atlas (TCGA) containing 13,198 lncRNAs from 539 patients. Differentially expressed lncRNAs were assessed using the R packages edgeR and DESeq. The prognostic significance of lncRNAs was measured using univariate Cox proportional hazards regression. ccRCC patients were then categorized into high- and low-score cohorts based on the cumulative distribution curve inflection point the of risk score, which was generated by the multivariate Cox regression model. Samples from the TCGA dataset were divided into training and validation subsets to verify the prognostic risk model. Bioinformatics methods, gene set enrichment analysis, and protein-protein interaction networks, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were subsequently used.
It was found that the risk score based on 6 novel lncRNAs (CTA-384D8.35, CTD-2263F21.1, LINC01510, RP11-352G9.1, RP11-395B7.2, RP11-426C22.4) exhibited superior prognostic value for ccRCC. Moreover, we categorized the cases into two groups (high-risk and low-risk), and also examined related pathways and genetic differences between them. Kaplan-Meier curves indicated that the median survival time of patients in the high-risk group was 73.5 months, much shorter than that of the low-risk group (112.6 months; P < 0.05). Furthermore, the risk score predicted the 5-year survival of all 539 ccRCC patients (AUC at 5 years, 0.683; concordance index [C-index], 0.853; 95% CI 0.817-0.889). The training set and validation set also showed similar performance (AUC at 5 years, 0.649 and 0.681, respectively; C-index, 0.822 and 0.891; 95% CI 0.774-0.870 and 0.844-0.938).
The results of this study can be applied to analyzing various prognostic factors, leading to new possibilities for clinical diagnosis and prognosis of ccRCC.
近几十年来，人们对长非编码 RNA（lncRNA）的科学认识有了提高。然而，对于 lncRNA 在透明细胞肾细胞癌（ccRCC）中的作用，研究甚少。更多的 lncRNA 被认为通过自身的分子机制影响 ccRCC 的进展。
本研究通过挖掘包含来自 539 名患者的 13198 个 lncRNA 的 TCGA 高通量 lncRNA-seq 数据，研究差异表达 lncRNA 的预后意义。使用 R 包 edgeR 和 DESeq 评估差异表达的 lncRNA。使用单因素 Cox 比例风险回归测量 lncRNA 的预后意义。然后，根据风险评分的累积分布曲线拐点，将 ccRCC 患者分为高得分和低得分队列，该风险评分由多因素 Cox 回归模型生成。来自 TCGA 数据集的样本被分为训练和验证子集，以验证预后风险模型。随后使用生物信息学方法、基因集富集分析、蛋白质-蛋白质相互作用网络、基因本体论和京都基因与基因组百科全书分析。
发现基于 6 个新 lncRNA（CTA-384D8.35、CTD-2263F21.1、LINC01510、RP11-352G9.1、RP11-395B7.2、RP11-426C22.4）的风险评分对 ccRCC 的预后具有更高的预测价值。此外，我们将病例分为两组（高风险和低风险），并检查了它们之间的相关途径和遗传差异。Kaplan-Meier 曲线表明，高风险组患者的中位生存时间为 73.5 个月，明显短于低风险组（112.6 个月；P < 0.05）。此外，风险评分预测了所有 539 例 ccRCC 患者的 5 年生存率（5 年 AUC，0.683；一致性指数[C-index]，0.853；95%CI 0.817-0.889）。训练集和验证集也表现出类似的性能（5 年 AUC，分别为 0.649 和 0.681；C-index，分别为 0.822 和 0.891；95%CI 0.774-0.870 和 0.844-0.938）。
本研究的结果可应用于分析各种预后因素，为 ccRCC 的临床诊断和预后提供新的可能性。
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