Da Rong, Wang Maode, Jiang Haitao, Wang Tuo, Wang Wei
Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Front Oncol. 2021 Jan 7;10:531968. doi: 10.3389/fonc.2020.531968. eCollection 2020.
Abnormal RAS/RAF signaling plays a critical role in glioma. Although it is known that the V600E mutation of v-raf murine viral oncogene homolog B1 ( ) and amplification ( ) both result in constitutive activation of the RAS/RAF pathway, whether and have different effects on the survival of glioma patients needs to be clarified. Using cBioPortal, we retrieved studies of both mutations and copy number variations of the gene in CNS/brain tumors and investigated data from 69 nonredundant glioma patients. The mutation group had significantly more male patients (64.00% vs. 36.84%; = 0.046) and a higher occurrence of glioblastoma multiforme (66.00% vs. 31.58%; = 0.013) compared to those in the other group. The group had significantly more patients with the mutant isocitrate dehydrogenase 1 and 2 () (73.68% vs. 18.00%; = 0.000), tumor protein p53 () (73.68% vs. 30.00%; = 0.002), and alpha thalassemia/mental retardation syndrome X linked () (63.16% vs. 18.00%; = 0.001) than the mutation group. The and cohort had lower overall survival compared with the and groups ( = 0.001) and the mutation cohort ( = 0.019), including the ( = 0.033) and ( = 0.029) groups, using Kaplan-Meier survival curves and the log rank (Mantel-Cox) test. The and genotype was found to be an independent predictive factor for glioma with mutation and using proportional hazard regression analysis (HR = 0.138, = 0.018). Our findings indicate that frequently occurs with , , and mutations. Adult patients with glioma with and had worse prognoses compared with those with mutation and and . This suggests that the assessment of the status of and in adult glioma/glioblastoma patients has prognostic value as these patients have relatively short survival times and may benefit from personalized targeted therapy using and/or MEK inhibitors.
异常的RAS/RAF信号传导在胶质瘤中起关键作用。虽然已知v-raf鼠类肉瘤病毒癌基因同源物B1（ ）的V600E突变和 扩增（ ）均导致RAS/RAF途径的组成性激活，但 和 对胶质瘤患者生存是否有不同影响仍有待阐明。我们使用cBioPortal检索了中枢神经系统/脑肿瘤中该基因的突变和拷贝数变异研究，并调查了69例非冗余胶质瘤患者的数据。与另一组相比， 突变组男性患者显著更多（64.00%对36.84%； = 0.046），多形性胶质母细胞瘤的发生率更高（66.00%对31.58%； = 0.013）。 组中携带异柠檬酸脱氢酶1和2（ ）突变、肿瘤蛋白p53（ ）突变以及X连锁的α地中海贫血/智力发育迟缓综合征（ ）的患者显著多于 突变组（分别为73.68%对18.00%； = 0.000；73.68%对30.00%； = 0.002；63.16%对18.00%； = 0.001）。使用Kaplan-Meier生存曲线和对数秩（Mantel-Cox）检验， 和 队列的总生存期低于 和 组（ = 0.001）以及 突变队列（ = 0.019），包括 组（ = 0.033）和 组（ = 0.029）。通过 比例风险回归分析发现， 和 基因型是伴有 突变和 的胶质瘤的独立预测因素（风险比 = 0.138， = 0.018）。我们的研究结果表明， 常与 、 和 突变同时发生。与伴有 突变以及 和 的成人胶质瘤患者相比，伴有 和 的成人胶质瘤患者预后更差。这表明评估成人胶质瘤/胶质母细胞瘤患者中 和 的状态具有预后价值，因为这些患者生存时间相对较短，可能受益于使用 和/或MEK抑制剂的个性化靶向治疗。
