Zuniga Rubén David Dos Reis, Carrijo Gabriel Sant'Ana, do Vale Matheus Rocha, Reis Beatriz da Costa Aguiar Alves, da Veiga Glaucia Raquel Luciano, de Aguiar Paulo Henrique Pires, Fonseca Fernando Luiz Affonso
Centro Universitário FMABC, São Paulo, Brazil.
Centro Universitário FMABC, São Paulo, Brazil.
World Neurosurg. 2025 Jun;198:123988. doi: 10.1016/j.wneu.2025.123988. Epub 2025 Apr 19.
Intracranial meningiomas are the most common primary tumors of the central nervous system. Although generally benign, some genetic alterations can induce aggressive behavior characterized by higher recurrence rates and reduced survival.
A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, using PubMed, EMBASE, Web of Science, and Scopus databases to identify studies published until November 2024. Studies investigating genetic alterations in meningiomas with prognostic data (recurrence or survival) and a minimum sample size of five patients were included. Data were extracted and analyzed independently by two reviewers.
Of 3032 studies identified, 20 met the inclusion criteria. The most frequently studied pathogenic variants were telomerase reverse transcriptase promoter (TERTp) and neurofibromatosis type 2 (NF2), both associated with shorter recurrence-free survival (RFS) and overall survival (OS), respectively TERTp RFS (hazard ratio [HR] 4.35, 95% confidence interval [CI] 2.87-6.60) and OS (HR 2.55, 95%CI 1.25-5.22), and NF2 RFS (HR 1.49, 95%CI 1.04-2.14) and OS (HR 2.98, 95% CI 1.37-6.49). Subgroup analysis suggested that the TERTp variant may be more predictive of lower survival for overall meningiomas (instead of World Health Organization III only), similar to NF2 variants. Additionally, Krüppel-like factor 4 was identified as a protective factor, while cyclin-dependent kinase inhibitor 2A/B was identified as a risk factor.
This systematic review highlights the importance of pathogenic variants, particularly TERTp and NF2, as prognostic markers in intracranial meningiomas. These findings underscore the potential of integrating genetic profiling into clinical practice to refine risk stratification and guide personalized therapeutic strategies, ultimately improving patient outcomes and quality of life.
颅内脑膜瘤是中枢神经系统最常见的原发性肿瘤。虽然通常为良性，但一些基因改变可导致侵袭性表现，其特征为复发率较高和生存率降低。
按照系统评价和Meta分析的首选报告项目指南进行系统评价和Meta分析，使用PubMed、EMBASE、科学网和Scopus数据库识别截至2024年11月发表的研究。纳入调查脑膜瘤基因改变并具有预后数据（复发或生存）且最小样本量为5例患者的研究。由两名审阅者独立提取和分析数据。
在识别出的3032项研究中，20项符合纳入标准。研究最频繁的致病变异是端粒酶逆转录酶启动子（TERTp）和2型神经纤维瘤病（NF2），两者分别与无复发生存期（RFS）缩短和总生存期（OS）缩短相关，TERTp的RFS（风险比[HR]4.35，95%置信区间[CI]2.87 - 6.60）和OS（HR 2.55，95%CI 1.25 - 5.22），以及NF2的RFS（HR 1.49，95%CI 1.04 - 2.14）和OS（HR 2.98，95%CI 1.37 - 6.49）。亚组分析表明，TERTp变异可能比NF2变异更能预测总体脑膜瘤（而非仅世界卫生组织III级）的较低生存率。此外， Kruppel样因子4被确定为保护因素，而细胞周期蛋白依赖性激酶抑制剂2A/B被确定为危险因素。
本系统评价强调了致病变异，特别是TERTp和NF2，作为颅内脑膜瘤预后标志物的重要性。这些发现强调了将基因谱分析整合到临床实践中的潜力，以优化风险分层并指导个性化治疗策略，最终改善患者预后和生活质量。
