PDF(Pubmed)
Abstract：
Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis.
摘要：
脑膜瘤是最常见的原发性脑肿瘤，许多研究已经评估了许多生物标志物的预后价值。结果往往不一致。目前,没有可靠的生物标志物可用于预测生存，复发,脑膜瘤患者在临床实践中的进展。本研究旨在评估基于免疫组织化学（IHC）的生物标志物对脑膜瘤患者的预后价值。截至2023年11月，在PubMed上进行了系统的文献检索，中部,CINAHLPlus,和Scopus数据库。两位作者独立回顾了已确定的相关研究，提取的数据，并评估了纳入研究的偏倚风险。采用总生存期(OS)的风险比(HR)和95%置信区间(CI)进行Meta分析。无复发生存率（RFS），无进展生存期（PFS）。使用预后研究质量（QUIPS）工具评估纳入研究的偏倚风险。本综述共纳入100项研究，共16,745例患者。作为预测脑膜瘤患者OS的有希望的标志物，Ki-67/MIB-1（HR=1.03，95CI1.02至1.05）与患者的不良预后相关。细胞周期蛋白A的过表达（HR=4.91，95CI1.38至17.44），拓扑异构酶IIα（TOP2A）（HR=4.90，95CI2.96至8.12），p53（HR=2.40，95CI1.73至3.34），血管内皮生长因子（VEGF）（HR=1.61，95CI1.36至1.90），和Ki-67（HR=1.33，95CI1.21至1.46），也被确定为脑膜瘤患者RFS不良的不良预后生物标志物。相反，孕激素受体(PR)和p21染色阳性与较长的RFS相关,被认为是脑膜瘤患者预后良好的生物标志物(HR=0.60,95%CI0.41~0.88,HR=1.89,95CI1.11~3.20).此外,Ki-67的高表达被确定为脑膜瘤患者PFS不良的预后生物标志物(HR=1.02,95CI1.00~1.04).虽然只有在单一研究中，KPNA2，CDK6，Cox-2，MCM7和PCNA被认为是高表达的其他标志物，与脑膜瘤患者的不良预后有关。总之,荟萃分析的结果表明，PR，细胞周期蛋白A,TOP2A,p21，p53，VEGF和Ki-67与脑膜瘤患者的生存呈正相关或负相关，可能是评估预后的有用生物标志物。
