Wang Yulin, Liu Xin, Guan Gefei, Zhao Weijiang, Zhuang Minghua
Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Department of Stomatology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Front Neurol. 2019 Jul 16;10:745. doi: 10.3389/fneur.2019.00745. eCollection 2019.
Glioblastoma (GBM) is the most common and fatal primary brain tumor in adults. It is necessary to identify novel and effective biomarkers or risk signatures for GBM patients. Differentially expressed genes (DEGs) between GBM and low-grade glioma (LGG) in TCGA samples were screened out and weight correlation network analysis (WGCNA) was performed to confirm WHO grade-related genes. Five genes were selected via multivariate Cox proportional hazards regression analysis and were used to construct a risk signature. A nomogram composed of the risk signature and clinical characters (age, radiotherapy, and chemotherapy experience) was established to predict 1, 3, 5-year survival rate for GBM patients. One hundred ninety-four DEGs in blue gene module were found to be positively related to WHO grade via WGCNA. Five genes (DES, RANBP17, CLEC5A, HOXC11, POSTN) were selected to construct a risk signature for GBM via R language. This risk signature was identified to independently predict the outcome of GBM patients, as well as stratified by IDH1 status, MGMT promoter status, and radio-chemotherapy. The nomogram was established which combined the risk signature with clinical factors. The results of c-index, ROC curve and calibration plot revealed the nomogram showing a good accuracy for predicting 1, 3, or 5-year survival of GBM patients. The risk signature with five genes could serve as an independent factor for predicting the prognosis of patients with GBM. Moreover, the nomogram with the risk signature and clinical traits proved to perform better for predicting 1, 3, 5-year survival rate.
胶质母细胞瘤(GBM)是成人中最常见且致命的原发性脑肿瘤。为GBM患者识别新的有效生物标志物或风险特征很有必要。筛选出TCGA样本中GBM与低级别胶质瘤(LGG)之间的差异表达基因(DEG),并进行加权基因共表达网络分析(WGCNA)以确认与世界卫生组织(WHO)分级相关的基因。通过多变量Cox比例风险回归分析选择了五个基因,并用于构建风险特征。建立了一个由风险特征和临床特征(年龄、放疗和化疗经历)组成的列线图,以预测GBM患者的1年、3年、5年生存率。通过WGCNA发现蓝色基因模块中的194个DEG与WHO分级呈正相关。通过R语言选择了五个基因(DES、RANBP17、CLEC5A、HOXC11、POSTN)来构建GBM的风险特征。该风险特征被确定为可独立预测GBM患者的预后,并可根据异柠檬酸脱氢酶1(IDH1)状态、O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子状态和放化疗进行分层。建立了将风险特征与临床因素相结合的列线图。一致性指数(c-index)、受试者工作特征曲线(ROC曲线)和校准图的结果显示,该列线图在预测GBM患者1年、3年或5年生存率方面具有良好的准确性。具有五个基因的风险特征可作为预测GBM患者预后的独立因素。此外,具有风险特征和临床特征的列线图在预测1年、3年、5年生存率方面表现更佳。