Wu Shan, Qiao Qiao, Li Guang
Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China.
Front Oncol. 2020 Jun 16;10:871. doi: 10.3389/fonc.2020.00871. eCollection 2020.
Glioma is the most common and fatal primary brain tumor that has a high risk of recurrence in adults. Identification of predictive biomarkers is necessary to optimize therapeutic strategies. This study investigated the predictive efficacy of a previously identified radiosensitivity signature as well as Exportin 1 (XPO1) expression levels. A total of 1,552 patients diagnosed with glioma were analyzed using the Chinese Glioma Genome Atlas and The Cancer Genome Atlas databases. The radiosensitive and radioresistant groups were identified based on a radiosensitivity signature. Patients were also stratified into XPO1-high and XPO1-low groups based on mRNA expression levels. Overall survival rates were compared across patient groups. Differential gene expression was detected and analyzed through pathway enrichment and Gene Set Enrichment Analysis (GSEA). To predict 1-, 3-, and 5-years survival rates for glioma patients, a nomogram was established combining the radiosensitivity gene signature, XPO1 status, and clinical characteristics. An artificial intelligence clustering system and a survival prediction system of glioma were developed to predict individual risk. This proposed classification based on a radiosensitivity gene signature and XPO1 expression levels provides an independent prognostic factor for glioma. The RR-XPO1-high group shows a poor prognosis and may benefit most from radiotherapy-combined anti-XPO1 treatment. The nomogram based on the radiosensitivity gene signature, XPO1 expression, and clinical characteristics performs more optimally compared to the WHO classification and IDH status in predicting survival rates for glioma patients. The online clustering and prediction systems make it accessible to predict risk and optimize treatment for a special patient. The cell cycle, p53, and focal adhesion pathways are associated with more invasive glioma cases. Combining the radiosensitivity signature and XPO1 expression is a favorable approach to predict outcomes as well as determine optimal therapeutic strategies for glioma patients.
胶质瘤是最常见且致命的原发性脑肿瘤,在成人中具有较高的复发风险。识别预测性生物标志物对于优化治疗策略至关重要。本研究调查了先前确定的放射敏感性特征以及核输出蛋白1(XPO1)表达水平的预测效力。使用中国胶质瘤基因组图谱和癌症基因组图谱数据库对总共1552例诊断为胶质瘤的患者进行了分析。基于放射敏感性特征确定放射敏感组和放射抵抗组。还根据mRNA表达水平将患者分层为XPO1高表达组和XPO1低表达组。比较各患者组的总生存率。通过通路富集和基因集富集分析(GSEA)检测并分析差异基因表达。为了预测胶质瘤患者的1年、3年和5年生存率,建立了一个结合放射敏感性基因特征、XPO1状态和临床特征的列线图。开发了一个人工智能聚类系统和一个胶质瘤生存预测系统来预测个体风险。这种基于放射敏感性基因特征和XPO1表达水平的分类方法为胶质瘤提供了一个独立的预后因素。RR-XPO1高表达组预后较差,可能从放疗联合抗XPO1治疗中获益最大。与世界卫生组织(WHO)分类和异柠檬酸脱氢酶(IDH)状态相比,基于放射敏感性基因特征、XPO1表达和临床特征的列线图在预测胶质瘤患者生存率方面表现更优。在线聚类和预测系统使预测特殊患者的风险和优化治疗变得可行。细胞周期、p53和粘着斑通路与侵袭性更强的胶质瘤病例相关。结合放射敏感性特征和XPO1表达是预测胶质瘤患者预后以及确定最佳治疗策略的一种有效方法。