Hu Li, Han Zhibin, Cheng Xingbo, Wang Sida, Feng Yumeng, Lin Zhiguo
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Genet. 2021 Feb 23;12:638458. doi: 10.3389/fgene.2021.638458. eCollection 2021.
Glioblastoma multiform (GBM) is a malignant central nervous system cancer with dismal prognosis despite conventional therapies. Scientists have great interest in using immunotherapy for treating GBM because it has shown remarkable potential in many solid tumors, including melanoma, non-small cell lung cancer, and renal cell carcinoma. The gene expression patterns, clinical data of GBM individuals from the Cancer Genome Atlas database (TCGA), and immune-related genes (IRGs) from ImmPort were used to identify differentially expressed IRGs through the Wilcoxon rank-sum test. The association between each IRG and overall survival (OS) of patients was investigated by the univariate Cox regression analysis. LASSO Cox regression assessment was conducted to explore the prognostic potential of the IRGs of GBM and construct a risk score formula. A Kaplan-Meier curve was created to estimate the prognostic role of IRGs. The efficiency of the model was examined according to the area under the receiver operating characteristic (ROC) curve. The TCGA internal dataset and two GEO external datasets were used for model verification. We evaluated IRG expression in GBM and generated a risk model to estimate the prognosis of GBM individuals with seven optimal prognostic expressed IRGs. A landscape of 22 types of tumor-infiltrating immune cells (TIICs) in glioblastoma was identified, and we investigated the link between the seven IRGs and the immune checkpoints. Furthermore, there was a correlation between the IRGs and the infiltration level in GBM. Our data suggested that the seven IRGs identified in this study are not only significant prognostic predictors in GBM patients but can also be utilized to investigate the developmental mechanisms of GBM and in the design of personalized treatments for them.
多形性胶质母细胞瘤(GBM)是一种恶性中枢神经系统癌症,尽管采用了传统疗法,但其预后仍然很差。科学家们对使用免疫疗法治疗GBM非常感兴趣,因为它在许多实体瘤中都显示出了显著的潜力,包括黑色素瘤、非小细胞肺癌和肾细胞癌。利用癌症基因组图谱数据库(TCGA)中GBM患者的基因表达模式、临床数据以及ImmPort中的免疫相关基因(IRG),通过Wilcoxon秩和检验来识别差异表达的IRG。通过单变量Cox回归分析研究每个IRG与患者总生存期(OS)之间的关联。进行LASSO Cox回归评估,以探索GBM的IRG的预后潜力并构建风险评分公式。绘制Kaplan-Meier曲线以评估IRG的预后作用。根据受试者工作特征(ROC)曲线下的面积来检验模型的效率。使用TCGA内部数据集和两个GEO外部数据集进行模型验证。我们评估了GBM中IRG的表达,并生成了一个风险模型,以估计具有七个最佳预后表达IRG的GBM患者的预后。确定了胶质母细胞瘤中22种肿瘤浸润免疫细胞(TIIC)的情况,并研究了这七个IRG与免疫检查点之间的联系。此外,IRG与GBM中的浸润水平之间存在相关性。我们的数据表明,本研究中确定的七个IRG不仅是GBM患者重要的预后预测指标,还可用于研究GBM的发病机制以及为其设计个性化治疗方案。