核转运相关基因特征与 IDH 突变和 1p/19q 联合缺失可更好地预测胶质瘤患者的预后。

BACKGROUND: The nuclear transport system has been proposed to be indispensable for cell proliferation and invasion in cancers. Prognostic biomarkers and molecular targets in nuclear transport systems have been developed. However, no systematic analysis of genes related to nuclear transport in gliomas has been performed. An integrated prognostic classification involving mutation and nuclear transport gene signatures has not yet been explored. METHODS: In the present study, we analyzed gliomas from a training cohort (TCGA dataset, n = 660) and validation cohort (CGGA dataset, n = 668) to develop a prognostic nuclear transport gene signature and generate an integrated classification system. Gene set enrichment analysis (GSEA) showed that glioblastoma (GBM) was mainly enriched in nuclear transport progress compared to lower-grade glioma (LGG). Then, we developed a nuclear transport risk score (NTRS) for gliomas with a training cohort. NTRS was significantly correlated with clinical and genetic characteristics, including grade, age, histology, IDH status and 1p/19q codeletion, in the training and validation cohorts. RESULTS: Survival analysis revealed that patients with a higher NTRS exhibited shorter overall survival. NTRS showed better prognostic value compared to classical molecular markers, including IDH status and 1p/19q codeletion. Furthermore, univariate and multivariate analyses indicated that NTRS was an independent prognostic factor for gliomas. Enrichment map and Gene Ontology analysis demonstrated that signaling pathways related to the cell cycle were enriched in the NTRS group. Subgroup survival analysis revealed that NTRS could differentiate the outcomes of low- and high-risk patients with wild-type IDH or mutant IDH and 1p/19q non-codeletion. CONCLUSIONS: NTRS is associated with poor outcomes and could be an independent prognostic marker in diffuse gliomas. Prognostic classification combined with IDH mutation, 1p/19q codeletion and NTRS could better predict the survival of glioma patients.

背景：核转运系统被认为对癌症中的细胞增殖和侵袭是不可或缺的。已经开发了核转运系统中的预后生物标志物和分子靶标。然而，尚未对神经胶质瘤中的核转运相关基因进行系统分析。涉及核转运基因突变和基因特征的综合预后分类尚未得到探索。

方法：在本研究中，我们分析了来自训练队列（TCGA 数据集，n=660）和验证队列（CGGA 数据集，n=668）的神经胶质瘤，以开发预后核转运基因特征并生成综合分类系统。基因集富集分析（GSEA）表明，与低级别神经胶质瘤（LGG）相比，胶质母细胞瘤（GBM）主要富集于核转运过程。然后，我们在训练队列中为神经胶质瘤开发了核转运风险评分（NTRS）。在训练和验证队列中，NTRS 与临床和遗传特征（包括分级、年龄、组织学、IDH 状态和 1p/19q 共缺失）显著相关。

结果：生存分析显示，NTRS 较高的患者总生存期较短。与经典分子标志物（包括 IDH 状态和 1p/19q 共缺失）相比，NTRS 显示出更好的预后价值。此外，单因素和多因素分析表明 NTRS 是神经胶质瘤的独立预后因素。富集图谱和基因本体论分析表明，NTRS 组中与细胞周期相关的信号通路被富集。亚组生存分析显示，NTRS 可以区分 IDH 野生型或突变型和 1p/19q 非共缺失的低风险和高风险患者的预后。

结论：NTRS 与不良预后相关，可能是弥漫性神经胶质瘤的独立预后标志物。联合 IDH 突变、1p/19q 共缺失和 NTRS 的预后分类可以更好地预测神经胶质瘤患者的生存。