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Identification and validation of a 21-mRNA prognostic signature in diffuse lower-grade gliomas.
Journal of Neuro-Oncology ( IF 3.2 ) Pub Date : 2019-12-18 , DOI: 10.1007/s11060-019-03372-z
Lai-Rong Song 1, 2, 3, 4 , Jian-Cong Weng 1, 2, 3, 4 , Xu-Lei Huo 1, 2, 3, 4 , Liang Wang 1, 2, 3, 4 , Huan Li 1, 3, 4 , Da Li 1, 2, 3, 4 , Zhen Wu 1, 2, 3, 4 , Jun-Ting Zhang 1, 2, 3, 4
Affiliation  

PURPOSE Diffuse low-grade and intermediate-grade gliomas, also known as lower-grade gliomas (LGGs), are a class of central nervous system tumors. Overall survival varies greatly between patients, highlighting the importance of evaluating exact outcomes to facilitate individualized clinical management. We aimed to identify an mRNA-based prognostic signature to predict the survival of patients with LGGs. METHODS A total of 874 LGGs from two public datasets were included. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the most prognostic mRNAs and build a risk score. A nomogram incorporating the risk score and clinical factors was established for individualized survival prediction. The performance of the nomogram was assessed in the training set (329 patients), internal validation set (140 patients), and external validation set (405 patients). RESULTS 21 most prognostic mRNAs remained following the LASSO Cox regression. The 21-mRNA signature successfully stratified patients into high- and low-risk groups (P < 0.001 for all datasets in Kaplan-Meier analysis). Subsequent gene set enrichment analysis identified 19 essential biological processes in high-risk LGGs. Furthermore, a nomogram incorporating the risk score, age, grade, and 1p/19q status was developed with favorable calibration and high predictive accuracy in the training set and validation sets (C-index: 0.877, 0.878, and 0.812, respectively). CONCLUSION The 21-mRNA signature has reliable prognostic value for LGGs and might facilitate the effective stratification and individualized management of patients.

中文翻译:

弥漫性低级神经胶质瘤中21-mRNA预后标记的鉴定和验证。

目的弥漫性低级和中级神经胶质瘤,也称为低级神经胶质瘤(LGGs),是一类中枢神经系统肿瘤。患者之间的总体存活率差异很大,突出了评估准确结果以促进个性化临床管理的重要性。我们旨在鉴定基于mRNA的预后标志,以预测LGG患者的生存情况。方法包括来自两个公共数据集的总共874个LGG。使用最小绝对收缩和选择算子(LASSO)Cox回归来选择最能预测预后的mRNA,并建立风险评分。建立了包含风险评分和临床因素的列线图,用于个体化生存预测。在培训组(329例),内部验证组(140例)中评估了列线图的性能,和外部验证集(405例患者)。结果LASSO Cox回归后,仍有21种预后最强的mRNA。21-mRNA标记成功地将患者分为高风险和低风险组(在Kaplan-Meier分析中,所有数据集的P <0.001)。随后的基因集富集分析确定了高危LGG中的19个基本生物学过程。此外,在训练集和验证集中开发了包含风险评分,年龄,等级和1p / 19q状态的列线图,具有良好的校准和较高的预测准确性(C指数分别为0.877、0.878和0.812)。结论21-mRNA标记对LGGs具有可靠的预后价值,可能有助于对患者进行有效的分层和个体化管理。结果LASSO Cox回归后,仍有21种预后最强的mRNA。21-mRNA标记成功地将患者分为高风险和低风险组(在Kaplan-Meier分析中,所有数据集的P <0.001)。随后的基因集富集分析确定了高危LGG中的19个基本生物学过程。此外,在训练集和验证集中开发了包含风险评分,年龄,等级和1p / 19q状态的列线图,具有良好的校准和较高的预测准确性(C指数分别为0.877、0.878和0.812)。结论21-mRNA标记对LGGs具有可靠的预后价值,可能有助于对患者进行有效的分层和个体化管理。结果LASSO Cox回归后,仍有21种预后最强的mRNA。21-mRNA标记成功地将患者分为高风险和低风险组(在Kaplan-Meier分析中,所有数据集的P <0.001)。随后的基因集富集分析确定了高危LGG中的19个基本生物学过程。此外,在训练集和验证集中开发了包含风险评分,年龄,等级和1p / 19q状态的列线图,具有良好的校准和较高的预测准确性(C指数分别为0.877、0.878和0.812)。结论21-mRNA标记对LGGs具有可靠的预后价值,可能有助于对患者进行有效的分层和个体化管理。21-mRNA标记成功地将患者分为高风险和低风险组(在Kaplan-Meier分析中,所有数据集的P <0.001)。随后的基因集富集分析确定了高危LGG中的19个基本生物学过程。此外,在训练集和验证集中开发了包含风险评分,年龄,等级和1p / 19q状态的列线图,具有良好的校准和较高的预测准确性(C指数分别为0.877、0.878和0.812)。结论21-mRNA标记对LGGs具有可靠的预后价值,可能有助于对患者进行有效的分层和个体化管理。21-mRNA标记成功地将患者分为高风险和低风险组(在Kaplan-Meier分析中,所有数据集的P <0.001)。随后的基因集富集分析确定了高危LGG中的19个基本生物学过程。此外,在训练集和验证集中开发了包含风险评分,年龄,等级和1p / 19q状态的列线图,具有良好的校准和较高的预测准确性(C指数分别为0.877、0.878和0.812)。结论21-mRNA标记对LGGs具有可靠的预后价值,可能有助于对患者进行有效的分层和个体化管理。在培训集和验证集中开发了包含风险评分,年龄,等级和1p / 19q状态的列线图,具有良好的校准和较高的预测准确性(C指数分别为0.877、0.878和0.812)。结论21-mRNA标记对LGGs具有可靠的预后价值,可能有助于对患者进行有效的分层和个体化管理。在培训集和验证集中开发了包含风险评分,年龄,等级和1p / 19q状态的列线图,具有良好的校准和较高的预测准确性(C指数分别为0.877、0.878和0.812)。结论21-mRNA标记对LGGs具有可靠的预后价值,可能有助于对患者进行有效的分层和个体化管理。
更新日期:2019-12-19
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