Development and Validation of a Liquid-Liquid Phase Separation-Related Gene Signature as Prognostic Biomarker for Low-Grade Gliomas.

4区医学 Q3 Medicine Disease Markers Pub Date : 2022-09-23 eCollection Date: 2022-01-01 DOI:10.1155/2022/1487165

Lidong Ning, Guanyan Zhao, Changji Xie, Huan Lan, Jiefei Chen, Hu Tan, ChengCong Wei, Zhiyu Zhou

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Abstract

Aim: To explore whether the liquid-liquid phase separation- (LLPS-) related genes were potential prognostic markers that could contribute to the further classification of low-grade gliomas (LGGs).

Methods: The LLPS-related genes were subjected to functional enrichment analysis. The univariable, least absolute shrinkage and selection operator, and multivariable stepwise Cox regression analyses were performed to develop an LLPS-related gene signature (GS) in the discovery data set. The biological characteristics of the high-risk LGG were explored using gene set enrichment analysis. Two independent external data sets were used to validate the LLPS-related GS.

Results: LLPS-related genes are involved in multiple important cancer-related biological processes and pathways in LGG. Nine LLPS-related genes were identified to construct the LLPS-related GS, which was significantly associated with the prognosis of LGG patients. The LLPS-related GS could successfully divide patients with LGG into high- and low-risk groups, and the high-risk group showed a poorer prognosis than the low-risk group. Furthermore, the LLPS-related GS was independent of IDH and 1p19q status. Several cancer-related pathways may be more active in high-risk LGGs, such as IL6 JAK STAT3 signaling pathway. The LLPS-related GS was successfully validated with two independent external data sets.

Conclusion: We developed and validated a novel LLPS-related GS for risk stratification of LGG. Our findings may provide more precise management for LGGs and a useful reference for LLPS mechanism to link LGG studies.

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液-液相分离相关基因标记作为低级别胶质瘤预后生物标志物的开发和验证。

目的:探讨液-液相分离- (LLPS-)相关基因是否为低级别胶质瘤(LGGs)进一步分类的潜在预后标志物。方法:对llps相关基因进行功能富集分析。通过单变量、最小绝对收缩和选择算子以及多变量逐步Cox回归分析，在发现数据集中建立llps相关基因特征(GS)。利用基因集富集分析探讨高危LGG的生物学特性。使用两个独立的外部数据集来验证llps相关的GS。结果:llps相关基因在LGG中参与多种重要的癌症相关生物学过程和途径。鉴定出9个llps相关基因，构建与LGG患者预后显著相关的llps相关GS。llps相关的GS可以成功地将LGG患者分为高危组和低危组，高危组的预后比低危组差。此外，llps相关的GS与IDH和1p19q状态无关。一些与癌症相关的通路可能在高风险的lgg中更活跃，如IL6 JAK STAT3信号通路。用两个独立的外部数据集成功验证了llps相关的GS。结论:我们开发并验证了一种用于LGG风险分层的新型llps相关GS。我们的研究结果可能为LGGs的更精确的管理提供帮助，并为LLPS机制连接LGG研究提供有益的参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Disease Markers 医学-病理学

自引率

0.00%

发文量

792

审稿时长

6-12 weeks

期刊介绍： Disease Markers is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.