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全基因组筛选和队列验证鉴定新型 lncRNAs 作为透明细胞肾细胞癌的预后生物标志物。

Genome-wide screening and cohorts validation identifying novel lncRNAs as prognostic biomarkers for clear cell renal cell carcinoma.

机构信息

Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

J Cell Biochem. 2020 Mar;121(3):2559-2570. doi: 10.1002/jcb.29478. Epub 2019 Oct 23.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the main subtype of renal cell carcinoma with varied prognosis. We aimed to identify and assess the possible prognostic long noncoding RNA (lncRNA) biomarkers. LncRNAs expression data and corresponding clinical information of 619 ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Differentially expressed genes analysis, univariate Cox regression, the least absolute shrinkage and selection operator Cox regression model were utilized to identify hub lncRNAs. Multivariate Cox regression was used to establish the risk model. Statistical analysis was performed using R 3.5.3. The expression value of five lncRNAs and the risk-score levels were significantly associated with a survival prognosis of ccRCC patients (all P < .001). In the TCGA validation cohort, the area under the curve (AUC) for the integrated nomogram was 0.905 and 0.91 for 3-, 5-year prediction separately. The AUC reached up to 0.757 in an independent ICGC cohort. Besides, the calibration plots also illustrated well curve-fitting between observation values and predictive values. Weighted gene co-expression network analysis and subsequent pathway analysis revealed that the PI3K-Akt-mTOR and hypoxia-inducible factor signaling crosstalk might function as the most essential mechanisms related to the five-lncRNAs signature. Our study suggested that lncRNA AC009654.1, AC092490.2, LINC00524, LINC01234, and LINC01885 were significantly associated with ccRCC prognosis. The prognostic model based on this five lncRNA may predict the overall survival of ccRCC.

摘要

透明细胞肾细胞癌(ccRCC)是肾细胞癌的主要亚型,具有不同的预后。我们旨在确定和评估可能的预后长链非编码 RNA(lncRNA)生物标志物。从癌症基因组图谱(TCGA)和国际癌症基因组联合会(ICGC)数据库中下载了 619 例 ccRCC 患者的 lncRNA 表达数据和相应的临床信息。使用差异表达基因分析、单变量 Cox 回归、最小绝对值收缩和选择算子 Cox 回归模型来识别关键 lncRNA。多变量 Cox 回归用于建立风险模型。使用 R 3.5.3 进行统计分析。五个 lncRNA 的表达值和风险评分水平与 ccRCC 患者的生存预后显著相关(均 P <.001)。在 TCGA 验证队列中,综合列线图的曲线下面积(AUC)分别为 0.905 和 0.91,用于 3 年和 5 年的预测。在独立的 ICGC 队列中,AUC 高达 0.757。此外,校准图也说明了观测值与预测值之间的良好曲线拟合。加权基因共表达网络分析和随后的通路分析表明,PI3K-Akt-mTOR 和缺氧诱导因子信号转导相互作用可能是与五个 lncRNA 特征相关的最重要的机制。我们的研究表明,lncRNA AC009654.1、AC092490.2、LINC00524、LINC01234 和 LINC01885 与 ccRCC 预后显著相关。基于这五个 lncRNA 的预后模型可能预测 ccRCC 的总生存率。

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