Jia Yanfei, Yang Wenzhen, Tang Bo, Feng Qian, Dong Zhiqiang
Department of Neurosurgery, Lanzhou University Second Hospital, No. 82 Cuiyingmen, Chengguan District, Lanzhou, Gansu Province 730000, China.
Department of Neurosurgery, Lanzhou University Second Hospital, No. 82 Cuiyingmen, Chengguan District, Lanzhou, Gansu Province 730000, China.
Transl Oncol. 2021 Jan;14(1):100979. doi: 10.1016/j.tranon.2020.100979. Epub 2020 Dec 5.
Our study attempted to identify hub genes related to isocitrate dehydrogenase (IDH) mutation in glioma and develop a prognostic model for IDH-mutant glioma patients. In a first step, ten hub genes significantly associated with the IDH status were identified by weighted gene coexpression analysis (WGCNA). The functional enrichment analysis demonstrated that the most enriched terms of these hub genes were cadherin binding and glutathione metabolism. Three of these hub genes were significantly linked with the survival of glioma patients. 328 samples of IDH-mutant glioma were separated into two datasets: a training set (N = 228) and a test set (N = 100). Based on the training set, we identified two IDH-mutant subtypes with significantly different pathological features by using consensus clustering. A 31 gene-signature was identified by the least absolute shrinkage and selection operator (LASSO) algorithm and used for establishing a differential prognostic model for IDH-mutant patients. In addition, the test set was employed for validating the prognostic model, and the model was proven to be of high value in classifying prognostic information of samples. The functional annotation revealed that the genes related to the model were mainly enriched in nuclear division, DNA replication, and cell cycle. Collectively, this study provided novel insights into the molecular mechanism of IDH mutation in glioma, and constructed a prognostic model which can be effective for predicting prognosis of glioma patients with IDH-mutation, which might promote the development of IDH target agents in glioma therapies and contribute to accurate prognostication and management in IDH-mutant glioma patients.
我们的研究试图鉴定与胶质瘤中异柠檬酸脱氢酶（IDH）突变相关的枢纽基因，并为IDH突变型胶质瘤患者建立一个预后模型。第一步，通过加权基因共表达分析（WGCNA）鉴定出与IDH状态显著相关的10个枢纽基因。功能富集分析表明，这些枢纽基因最富集的术语是钙黏蛋白结合和谷胱甘肽代谢。其中3个枢纽基因与胶质瘤患者的生存显著相关。将328例IDH突变型胶质瘤样本分为两个数据集：训练集（N = 228）和测试集（N = 100）。基于训练集，我们通过一致性聚类鉴定出两种具有显著不同病理特征的IDH突变亚型。通过最小绝对收缩和选择算子（LASSO）算法鉴定出一个31基因特征，并用于建立IDH突变患者的差异预后模型。此外，使用测试集对预后模型进行验证，结果证明该模型在分类样本的预后信息方面具有很高的价值。功能注释显示，与该模型相关的基因主要富集在核分裂、DNA复制和细胞周期中。总的来说，本研究为胶质瘤中IDH突变的分子机制提供了新的见解，并构建了一个可有效预测IDH突变型胶质瘤患者预后的预后模型，这可能会促进胶质瘤治疗中IDH靶向药物的开发，并有助于IDH突变型胶质瘤患者的准确预后评估和管理。
