Xu Jie, Liu Fang, Li Yuntao, Shen Liang
Department of Neurosurgery, Huzhou Cent Hospital, Affiliated Cent Hospital Huzhou University, 198 Hongqi Road, Huzhou, 313000, Zhejiang, China.
Department of Neurosurgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, 68 Gehu Road, Changzhou, 213000, Jiangsu, China.
Cell Mol Neurobiol. 2022 Apr;42(3):709-722. doi: 10.1007/s10571-020-00959-3. Epub 2020 Sep 7.
Lower grade gliomas (LGGs) with codeletion of chromosomal arms 1p and 19q (1p/19 codeletion) have a favorable outcome. However, its overall survival (OS) varies. Here, we established an immune signature associated with 1p/19q codeletion for accurate prediction of prognosis of LGGs. The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases with RNA sequencing and corresponding clinical data were dichotomized into training group and testing group. The immune-related differentially expressed genes (DEGs) associated with 1p/19q codeletion were screened using Cox proportional hazards regression analyses. A prognostic signature was established using dataset from CGGA and tested in TCGA database. Subsequently, we explored the correlation between the prognostic signature and immune response. Thirteen immune genes associated with 1p/19q codeletion were used to construct a prognostic signature. The 1-, 3-, 5-year survival rates of the low-risk group were approximately 97%, 89%, and 79%, while those of the high-risk group were 81%, 50% and 34%, respectively, in the training group. The nomogram which comprised age, WHO grade, primary or recurrent types, 1p/19q codeletion status and risk score provided accurate prediction for the survival rate of glioma. DEGs that were highly expressed in the high-risk group clustered with many immune-related pathways. Immune checkpoints including TIM3, PD1, PDL1, CTLA4, TIGIT, MIR155HG, and CD48 were correlated with the risk score. VAV3 and TNFRFSF11B were found to be candidate immune checkpoints associated with prognosis. The 1p/19q codeletion-associated immune signature provides accurate prediction of OS. VAV3 and TNFRFSF11B are novel immune checkpoints.
染色体臂1p和19q共缺失(1p/19共缺失)的低级别胶质瘤(LGG)预后良好。然而,其总生存期(OS)存在差异。在此,我们建立了一种与1p/19共缺失相关的免疫特征,用于准确预测LGG的预后。将具有RNA测序和相应临床数据的中国胶质瘤基因组图谱(CGGA)和癌症基因组图谱(TCGA)数据库分为训练组和测试组。使用Cox比例风险回归分析筛选与1p/19共缺失相关的免疫相关差异表达基因(DEG)。利用CGGA数据集建立预后特征,并在TCGA数据库中进行测试。随后,我们探讨了预后特征与免疫反应之间的相关性。使用13个与1p/19共缺失相关的免疫基因构建预后特征。在训练组中,低风险组的1年、3年、5年生存率分别约为97%、89%和79%,而高风险组的生存率分别为81%、50%和34%。包含年龄、世界卫生组织分级、原发或复发类型、1p/19共缺失状态和风险评分的列线图为胶质瘤的生存率提供了准确预测。在高风险组中高表达的DEG与许多免疫相关途径聚集在一起。包括TIM3、PD1、PDL1、CTLA4、TIGIT、MIR155HG和CD48在内的免疫检查点与风险评分相关。发现VAV3和TNFRFSF11B是与预后相关的候选免疫检查点。1p/19共缺失相关的免疫特征可准确预测OS。VAV3和TNFRFSF11B是新的免疫检查点。