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构建并验证自噬相关长非编码 RNA 标志物用于预测肾透明细胞癌患者的预后

Construction and validation of an autophagy-related long noncoding RNA signature for prognosis prediction in kidney renal clear cell carcinoma patients.

机构信息

Department of medical college, Southeast University, Nanjing, China.

Department of Urology, Southeast University Zhongda hospital, Nanjing, China.

出版信息

Cancer Med. 2021 Apr;10(7):2359-2369. doi: 10.1002/cam4.3820. Epub 2021 Mar 2.

Abstract

PURPOSE

The purpose of this study was to identify autophagy-associated long noncoding RNAs (ARlncRNAs) using the kidney renal clear cell carcinoma (KIRC) patient data from The Cancer Genome Atlas (TCGA) database and to construct a prognostic risk-related ARlncRNAs signature to accurately predict the prognosis of KIRC patients.

METHODS

The KIRC patient data were originated from TCGA database and were classified into a training set and testing set. Seven prognostic risk-related ARlncRNAs, identified using univariate, lasso, and multivariate Cox regression analysis, were used to construct prognostic risk-related signatures. Kaplan-Meier curves and receiver operating characteristic (ROC) curves as well as independent prognostic factor analysis and correlation analysis with clinical characteristics were utilized to evaluate and verify the specificity and sensitivity of the signature in training set and testing set, respectively. Two nomograms were established to predict the probable 1-, 3-, and 5-year survival of the KIRC patients. In addition, the lncRNA-mRNA co-expression network was constructed and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to identify biological functions of ARlncRNAs.

RESULTS

We constructed and verified a prognostic risk-related ARlncRNAs signature in training set and testing set, respectively. We found the survival time of KIRC patients with low-risk scores was significantly better than those with high-risk scores in training set and testing set. ROC curves suggested that the area under the ROC (AUC) value for prognostic risk score signature was 0.81 in training set and 0.705 in testing set. And AUC values corresponding to 1-, 3-, and 5 years of OS were 0.809, 0.753, and 0.794 in training set and 0.698, 0.682, and 0.754 in testing set, respectively. We established the two nomograms that confirmed high C-index and accomplished good prediction accuracy.

CONCLUSIONS

We constructed a prognostic risk-related ARlncRNAs signature that could accurately predict the prognosis of KIRC patients.

摘要

目的

本研究旨在利用癌症基因组图谱(TCGA)数据库中的肾透明细胞癌(KIRC)患者数据,鉴定自噬相关长非编码 RNA(ARlncRNA),并构建预后相关 ARlncRNA 特征,以准确预测 KIRC 患者的预后。

方法

KIRC 患者数据来源于 TCGA 数据库,并分为训练集和测试集。使用单因素、lasso 和多因素 Cox 回归分析鉴定出 7 个与预后相关的 ARlncRNA,用于构建预后相关的特征。通过 Kaplan-Meier 曲线和接受者操作特征(ROC)曲线以及独立预后因素分析和与临床特征的相关性分析,分别在训练集和测试集中评估和验证特征的特异性和敏感性。建立了两个列线图来预测 KIRC 患者可能的 1、3 和 5 年生存率。此外,构建了 lncRNA-mRNA 共表达网络,并进行了基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)分析,以鉴定 ARlncRNA 的生物学功能。

结果

我们分别在训练集和测试集中构建和验证了预后相关的 ARlncRNA 特征。我们发现,在训练集和测试集中,低风险评分的 KIRC 患者的生存时间明显优于高风险评分的患者。ROC 曲线表明,预后风险评分特征的 ROC 曲线下面积(AUC)在训练集中为 0.81,在测试集中为 0.705。在训练集中,1、3 和 5 年 OS 的 AUC 值分别为 0.809、0.753 和 0.794,在测试集中,AUC 值分别为 0.698、0.682 和 0.754。我们建立了两个列线图,证实了高 C 指数和良好的预测准确性。

结论

我们构建了一个与预后相关的 ARlncRNA 特征,可以准确预测 KIRC 患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45a9/7982638/430b20b0d4e3/CAM4-10-2359-g003.jpg

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