ABSTRACT

Objective: This study was designed to conduct molecular classification based on IDH1/2, TERT, ATRX, and DAXX changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups.

Methods: We analyzed the expression profiles of ATRX/DAXX and MALAT1 using the qRT-PCR method and IDH and TERT mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients.

Results: IDH1 mutation was observed in 5 (5.88%) and TERT mutation in 65 (76.47%) primary pediatric and adult GB patients. ATRX and DAXX were detected in 18 (21.18%) and 7 (8.24%) patients. TERT mutation and loss of ATRX/DAXX were associated with short overall survival (p < 0.001, p < 0.001, respectively). Patients carrying especially TERT C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001).

Conclusions: Our findings highlight that the presence of TERT C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.

摘要

目的：本研究旨在根据儿童和成人原发性胶质母细胞瘤 (GB) 中的IDH1/2、TERT、ATRX和DAXX变化进行分子分类，并分析 LncRNA MALAT1 在确定的同质亚组中的潜在相互作用。

方法：我们使用 qRT-PCR 方法分析了ATRX/DAXX和 MALAT1的表达谱，并使用 DNA 测序分析了 85 名原发性儿科和成人 GB 患者的IDH和TERT突变状态。

结果： 在 5 例（5.88%）中观察到IDH1突变，在 65 例（76.47%）原发性儿科和成人 GB 患者中观察到TERT突变。在 18 名 (21.18%) 和 7 名 (8.24%) 患者中检测到ATRX和DAXX 。TERT突变和ATRX/DAXX 缺失与较短的总生存期相关（分别为 p < 0.001，p < 0.001）。携带特别是TERT C228T 突变的患者预后较差（p < 0.001）。从遗传分析中获得了六个亚组。在亚组中，MALAT1 在具有单个TERT的 A 组中高度表达与 D 组和 E 组相比的突变（分别为 p = 0.001 和 p < 0.001）；此外，高 MALAT1 表达与 C228T 突变患者的预后较差相关（p < 0.001）。

结论：我们的研究结果强调了TERT C228T 突变的存在和 MALAT1 的表达可用作原发性 GB 患者随访和开发新治疗策略的主要目标。