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弥漫性胶质瘤中与临床预后相关的能量代谢相关特征的鉴定

Identification of an energy metabolism-related signature associated with clinical prognosis in diffuse glioma.

作者信息

Zhou Zhengui, Huang Ruoyu, Chai Ruichao, Zhou Xiaohong, Hu Zhiping, Wang Wenbiao, Chen Baoguo, Deng Lintao, Liu Yuqing, Wu Fan

机构信息

Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China.

Department of Cerebral Surgery, The People's Hospital of Gongan County. Hu Bei, Gongan, 434300, China.

出版信息

Aging (Albany NY). 2018 Nov 8;10(11):3185-3209. doi: 10.18632/aging.101625.

Abstract

Now, numerous exciting findings have been yielded in the field of energy metabolism within glioma cells. In addition to aerobic glycolysis, multiple catabolic pathways are employed for energy production. However, the prognostic significance of energy metabolism in glioma remains obscure. Here, we explored the relationship between energy metabolism gene profile and outcome of diffuse glioma patients using The Cancer Genome Altas (TCGA) and Chinese Glioma Genome Altas (CGGA) datasets. Based on the gene expression profile, consensus clustering identified two robust clusters of glioma patients with distinguished prognostic and molecular features. With the Cox proportional hazards model with elastic net penalty, an energy metabolism-related signature was built to evaluate patients' prognosis. Kaplan-Meier analysis found that the acquired signature could differentiate the outcome of low and high-risk groups of patients in both cohorts. Moreover, the signature, significantly associated with the clinical and molecular features, could serve as an independent prognostic factor for glioma patients. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) showed that gene sets correlated with high-risk group were involved in immune and inflammatory response, with the low-risk group were mainly related to glutamate receptor signaling pathway. Our results provided new insight into energy metabolism role in diffuse glioma.

摘要

目前,胶质瘤细胞能量代谢领域已取得众多令人振奋的研究成果。除有氧糖酵解外,多种分解代谢途径也用于能量产生。然而,胶质瘤中能量代谢的预后意义仍不明确。在此,我们利用癌症基因组图谱(TCGA)和中国胶质瘤基因组图谱(CGGA)数据集,探讨了能量代谢基因谱与弥漫性胶质瘤患者预后之间的关系。基于基因表达谱,一致性聚类识别出具有不同预后和分子特征的两个稳定的胶质瘤患者集群。通过带有弹性网络惩罚的Cox比例风险模型,构建了一个能量代谢相关特征来评估患者的预后。Kaplan-Meier分析发现,所获得的特征能够区分两个队列中低风险组和高风险组患者的预后。此外,该特征与临床和分子特征显著相关,可作为胶质瘤患者的独立预后因素。基因本体论(GO)和基因集富集分析(GSEA)表明,与高风险组相关的基因集参与免疫和炎症反应,而与低风险组相关的基因集主要与谷氨酸受体信号通路有关。我们的研究结果为能量代谢在弥漫性胶质瘤中的作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad12/6286858/98e309a7fb39/aging-10-101625-g001.jpg

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