Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Beijing, China.
Chinese Glioma Genome Atlas Network (CGGA), Beijing, China.
Cancer Sci. 2019 Jan;110(1):321-333. doi: 10.1111/cas.13878. Epub 2018 Dec 17.
Metabolic reprogramming has been proposed to be a hallmark of cancer. Aside from the glycolytic pathway, the metabolic changes of cancer cells primarily involve amino acid metabolism. However, in glioma, the characteristics of the amino acid metabolism-related gene set have not been systematically profiled. In the present study, RNA sequencing expression data from 309 patients in the Chinese Glioma Genome Atlas database were included as a training set, while another 550 patients within The Cancer Genome Atlas database were used to validate. Consensus clustering of the 309 samples yielded two robust groups. Compared with Cluster1, Cluster2 correlated with a better clinical outcome. We then developed an amino acid metabolism-related risk signature for glioma. Our results showed that patients in the high-risk group had dramatically shorter overall survival than low-risk counterparts in any subgroup, stratified by isocitrate dehydrogenase and 1p/19q status based on the 2016 World Health Organization classification guidelines. The 30-gene signature showed better prognostic value than the traditional factors "age" and "grade" by analyzing the receiver operating characteristic curve with areas under curve of 0.966, 0.692, 0.898 and 0.975, 0.677, 0.885 for 3- and 5-year survival, respectively. Moreover, univariate and multivariate analysis showed that the 30-gene signature was an independent prognostic factor for glioma. Furthermore, Gene Ontology analysis and Gene Set Enrichment Analysis showed that tumors with a high risk score correlated with various aspects of the malignancy of glioma. In summary, we demonstrated a novel amino acid metabolism-related risk signature for predicting prognosis for glioma.
代谢重编程被认为是癌症的一个标志。除了糖酵解途径外,癌细胞的代谢变化主要涉及氨基酸代谢。然而,在神经胶质瘤中,氨基酸代谢相关基因集的特征尚未得到系统分析。在本研究中,纳入了来自中国神经胶质瘤基因组图谱数据库的 309 名患者的 RNA 测序表达数据作为训练集,而来自癌症基因组图谱数据库的另外 550 名患者用于验证。对 309 个样本进行共识聚类,得到了两个稳健的组。与 Cluster1 相比,Cluster2 与更好的临床结果相关。然后,我们开发了一个用于神经胶质瘤的氨基酸代谢相关风险特征。我们的结果表明,在任何亚组中,高风险组的患者的总生存期明显短于低风险组,这些亚组根据 2016 年世界卫生组织分类指南,基于异柠檬酸脱氢酶和 1p/19q 状态进行分层。通过分析接受者操作特征曲线,30 基因特征比传统因素“年龄”和“分级”具有更好的预后价值,曲线下面积分别为 0.966、0.692、0.898 和 0.975、0.677、0.885,用于 3 年和 5 年生存率。此外,单因素和多因素分析表明,30 基因特征是神经胶质瘤的独立预后因素。此外,基因本体论分析和基因集富集分析表明,风险评分较高的肿瘤与神经胶质瘤恶性程度的各个方面相关。总之,我们证明了一种用于预测神经胶质瘤预后的新型氨基酸代谢相关风险特征。