Kun Sun, Duan Qiwen, Liu Gang, Lu Jing-Min
Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
Department of Oncology, Taihe Hospital, Hubei University of Medicine, Hubei, China.
Oncotarget. 2017 Apr 27;8(35):58222-58230. doi: 10.18632/oncotarget.17452. eCollection 2017 Aug 29.
Abnormal expression of DNA repair genes is frequently associated with cancerogenesis of many tumors, however, the role DNA repair genes play in the progression of glioblastoma remains unclear. In this study, taking advantage of large scale of RNA-seq data, as well as clinical data, the function and prognosis value of key DNA repair genes in glioblastoma were analyzed by systematically bioinformatic approaches. Clustering was performed to screen potentially abnormal DNA repair genes related to the prognosis of glioblastoma, followed by unsupervised clustering to identify molecular subtypes of glioblastomas. Characteristics and prognosis differences were analyzed among these molecular subtypes, and modular driver genes in molecular subtypes were identified based on changes in expression correlation. Multifactor Cox proportional hazard analysis was used to find the independent prognostic factor. A total of 15 key genes, which were significantly related to prognosis, were identified and four molecular subtypes of disease were obtained through unsupervised clustering, based on these 15 genes. By analyzing the clinical features of these 4 molecular subtypes, Cluster 4 was found to be different from others in terms of age and prognosis level. A total of 5 key DNA repair genes, CDK7, DDB2, RNH1, RFC2 and FAH, were screened to be significantly related to the prognosis of glioblastomas ( = 9.74e). In summary, the DNA repair genes which can predict the prognosis of patients with Glioblastoma multiforme (GBM) were identified and validated. The expression level of DNA repair genes shows the potential of predicting the prognosis and therapy design in targeting GBM.
DNA修复基因的异常表达常与多种肿瘤的发生相关,然而,DNA修复基因在胶质母细胞瘤进展中所起的作用仍不清楚。在本研究中,利用大规模RNA测序数据以及临床数据,通过系统的生物信息学方法分析了胶质母细胞瘤中关键DNA修复基因的功能和预后价值。进行聚类以筛选与胶质母细胞瘤预后相关的潜在异常DNA修复基因,随后进行无监督聚类以鉴定胶质母细胞瘤的分子亚型。分析了这些分子亚型之间的特征和预后差异,并根据表达相关性的变化鉴定了分子亚型中的模块化驱动基因。采用多因素Cox比例风险分析来寻找独立预后因素。共鉴定出15个与预后显著相关的关键基因,并基于这15个基因通过无监督聚类获得了疾病的四种分子亚型。通过分析这4种分子亚型的临床特征,发现聚类4在年龄和预后水平方面与其他亚型不同。共筛选出5个关键DNA修复基因CDK7、DDB2、RNH1、RFC2和FAH与胶质母细胞瘤的预后显著相关(=9.74e)。总之,鉴定并验证了可预测多形性胶质母细胞瘤(GBM)患者预后的DNA修复基因。DNA修复基因的表达水平显示出预测GBM预后和指导治疗设计的潜力。