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基于TCGA和CGGA的胶质母细胞瘤五lncRNA特征衍生风险评分:治疗评估和预后预测的潜在前景

A Five-lncRNAs Signature-Derived Risk Score Based on TCGA and CGGA for Glioblastoma: Potential Prospects for Treatment Evaluation and Prognostic Prediction.

作者信息

Niu Xuegang, Sun Jiangnan, Meng Lingyin, Fang Tao, Zhang Tongshuo, Jiang Jipeng, Li Huanming

机构信息

Department of Neurosurgery, Tianjin 4th Central Hospital, Tianjin, China.

Department of Psychiatry, Characteristic Medical Center of the Chinese People's Armed Police Force, Tianjin, China.

出版信息

Front Oncol. 2020 Dec 17;10:590352. doi: 10.3389/fonc.2020.590352. eCollection 2020.

Abstract

Accumulating studies have confirmed the crucial role of long non-coding RNAs (ncRNAs) as favorable biomarkers for cancer diagnosis, therapy, and prognosis prediction. In our recent study, we established a robust model which is based on multi-gene signature to predict the therapeutic efficacy and prognosis in glioblastoma (GBM), based on Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. lncRNA-seq data of GBM from TCGA and CGGA datasets were used to identify differentially expressed genes (DEGs) compared to normal brain tissues. The DEGs were then used for survival analysis by univariate and multivariate COX regression. Then we established a risk score model, depending on the gene signature of multiple survival-associated DEGs. Subsequently, Kaplan-Meier analysis was used for estimating the prognostic and predictive role of the model. Gene set enrichment analysis (GSEA) was applied to investigate the potential pathways associated to high-risk score by the R package "cluster profile" and Wiki-pathway. And five survival associated lncRNAs of GBM were identified: LNC01545, WDR11-AS1, NDUFA6-DT, FRY-AS1, TBX5-AS1. Then the risk score model was established and shows a desirable function for predicting overall survival (OS) in the GBM patients, which means the high-risk score significantly correlated with lower OS both in TCGA and CGGA cohort. GSEA showed that the high-risk score was enriched with PI3K-Akt, VEGFA-VEGFR2, TGF-beta, Notch, T-Cell pathways. Collectively, the five-lncRNAs signature-derived risk score presented satisfactory efficacies in predicting the therapeutic efficacy and prognosis in GBM and will be significant for guiding therapeutic strategies and research direction for GBM.

摘要

越来越多的研究证实了长链非编码RNA(lncRNAs)作为癌症诊断、治疗和预后预测的良好生物标志物的关键作用。在我们最近的研究中,基于中国胶质瘤基因组图谱(CGGA)和癌症基因组图谱(TCGA)数据库,我们建立了一个基于多基因特征的强大模型,用于预测胶质母细胞瘤(GBM)的治疗效果和预后。使用来自TCGA和CGGA数据集的GBM的lncRNA-seq数据来识别与正常脑组织相比的差异表达基因(DEGs)。然后通过单变量和多变量COX回归对DEGs进行生存分析。然后,我们根据多个生存相关DEGs的基因特征建立了一个风险评分模型。随后,使用Kaplan-Meier分析来评估该模型的预后和预测作用。基因集富集分析(GSEA)应用R包“cluster profile”和Wiki通路来研究与高风险评分相关的潜在通路。并鉴定出GBM的五个生存相关lncRNAs:LNC01545、WDR11-AS1、NDUFA6-DT、FRY-AS1、TBX5-AS1。然后建立了风险评分模型,该模型在预测GBM患者的总生存期(OS)方面显示出理想的功能,这意味着在TCGA和CGGA队列中,高风险评分与较低的OS显著相关。GSEA表明,高风险评分富含PI3K-Akt、VEGFA-VEGFR2、TGF-β、Notch、T细胞通路。总的来说,五个lncRNAs特征衍生的风险评分在预测GBM的治疗效果和预后方面表现出令人满意的效果,这对于指导GBM的治疗策略和研究方向具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8de/7773845/494fa2d04d40/fonc-10-590352-g001.jpg

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