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用于预测脑膜瘤患者预后的生物标志物：系统评价和荟萃分析。

Biomarkers for prognosis of meningioma patients: A systematic review and meta-analysis.

机构信息

Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.

Department of Epidemiology and Biostatistics, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand.

出版信息

PLoS One. 2024 May 17;19(5):e0303337. doi: 10.1371/journal.pone.0303337. eCollection 2024.

DOI:10.1371/journal.pone.0303337
PMID:38758750
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11101050/
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，但结果往往不一致。目前，没有可靠的生物标志物可用于预测脑膜瘤患者的生存、复发和进展。本研究旨在评估基于免疫组织化学（IHC）的脑膜瘤患者生物标志物的预后价值。截至 2023 年 11 月，我们在 PubMed、CENTRAL、CINAHL Plus 和 Scopus 数据库中进行了系统的文献检索。两位作者独立审查了确定的相关研究，提取数据，并评估了纳入研究的偏倚风险。使用风险比（HR）和 95%置信区间（CI）进行了总体生存（OS）、无复发生存（RFS）和无进展生存（PFS）的荟萃分析。使用预后研究质量（QUIPS）工具评估纳入研究的偏倚风险。本综述共纳入了 100 项研究，涉及 16745 名患者。Ki-67/MIB-1（HR=1.03，95%CI 1.02 至 1.05）被确定为与脑膜瘤患者 OS 不良相关的有前途的标志物，可用于预测患者的预后。Cyclin A（HR=4.91，95%CI 1.38 至 17.44）、拓扑异构酶 IIα（TOP2A）（HR=4.90，95%CI 2.96 至 8.12）、p53（HR=2.40，95%CI 1.73 至 3.34）、血管内皮生长因子（VEGF）（HR=1.61，95%CI 1.36 至 1.90）和 Ki-67（HR=1.33，95%CI 1.21 至 1.46）也被确定为脑膜瘤患者 RFS 不良的不利预后生物标志物。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%CI 0.41 至 0.88 和 HR=1.89，95%CI 1.11 至 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=1.02，95%CI 1.00 至 1.04）。尽管仅在单项研究中，KPNA2、CDK6、Cox-2、MCM7 和 PCNA 被提出为与脑膜瘤患者不良预后相关的高表达的额外标志物。总之，荟萃分析的结果表明，PR、cyclin 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。

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