Zou Han, Li Chang, Wanggou Siyi, Li Xuejun
Xiangya School of Medicine, Central South University, 172 Tongzipo Road, Changsha, Hunan 410013, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China.
J Cancer. 2020 Apr 27;11(15):4297-4307. doi: 10.7150/jca.43805. eCollection 2020.
Gliomas have been classified into different molecular subtypes based on their molecular features. To explore the prognostic factors of different subtypes of gliomas, we performed a univariate survival analysis based on the RNA-seq data of 653 patients obtained from The Cancer Genome Atlas. We identified 12205 (20.18%), 6125 (10.13%) and 5206 (8.61%) genes associated with the overall survival (OS) of the IDH-wildtype, IDH-mutation 1p/19q intact and IDH-mutation 1p/19q codeletion gliomas, respectively. Pathway enrichment analysis revealed that OS related genes were mainly involved in alcoholism, systemic lupus erythematosus, hematopoietic cell lineage and diabetes. The OS related genes were further selected using Lasso regression, and three prognostic risk score models were constructed to effectively predict the OS of the patients with different subtypes of gliomas. In total, 76 signature genes were identified and were selected to construct the three models. Moreover, neither of the 76 genes overlapped between different models, which suggested the enormous difference among the three subtypes, although some signature genes (SERPINA5, RP11.229A12.2 and RP11.62F24.2) were also identified as the OS related genes in different glioma subtypes. Interestingly, five genes (RP11.229A12.2, RP11.62F24.2, C3orf67, RP11.275H4.1 and TBX3) played opposing roles (protective or risk factor) in different subtypes. Additionally, the prognosis models consisted of a substantial proportion of non-coding RNA (58.74%, 70.13% and 58.11% in the IDH-wildtype, IDH-mutation 1p/19q intact and IDH-mutation 1p/19q codeletion). Furthermore, multivariate analysis integrating clinical variables demonstrated that risk group predicted by the prognostic models was an independent prognostic factor for gliomas. In conclusion, we have constructed and validated three models that have the potential to predict the prognosis of glioma patients. The genes and pathways identified in this study require further investigation for their underlying mechanisms and potential clinical significance in improving the OS of the glioma patients.
胶质瘤已根据其分子特征被分为不同的分子亚型。为了探索不同亚型胶质瘤的预后因素，我们基于从癌症基因组图谱获取的653例患者的RNA测序数据进行了单变量生存分析。我们分别鉴定出与异柠檬酸脱氢酶（IDH）野生型、IDH突变且1p/19q完整以及IDH突变且1p/19q共缺失的胶质瘤的总生存期（OS）相关的基因12205个（20.18%）、6125个（10.13%）和5206个（8.61%）。通路富集分析显示，与OS相关的基因主要涉及酒精中毒、系统性红斑狼疮、造血细胞谱系和糖尿病。使用套索回归进一步筛选与OS相关的基因，并构建了三个预后风险评分模型，以有效预测不同亚型胶质瘤患者的OS。总共鉴定出76个特征基因，并选择它们来构建这三个模型。此外，这76个基因在不同模型之间均无重叠，这表明这三种亚型之间存在巨大差异，尽管一些特征基因（丝氨酸蛋白酶抑制剂A5、RP11.229A12.2和RP11.62F24.2）在不同的胶质瘤亚型中也被鉴定为与OS相关的基因。有趣的是，五个基因（RP11.229A12.2、RP11.62F24.2、C3orf67、RP11.275H4.1和TBX3）在不同亚型中发挥着相反的作用（保护或风险因素）。此外，预后模型包含相当比例的非编码RNA（在IDH野生型、IDH突变1p/19q完整和IDH突变1p/19q共缺失的模型中分别为58.74%、70.13%和58.11%）。此外，整合临床变量的多变量分析表明，预后模型预测的风险组是胶质瘤的独立预后因素。总之，我们构建并验证了三个有可能预测胶质瘤患者预后的模型。本研究中鉴定出的基因和通路，其潜在机制以及在改善胶质瘤患者OS方面的潜在临床意义需要进一步研究。
