一种靶向基因表达生物标志物可预测临床低风险脑膜瘤复发。

A targeted gene expression biomarker predicts clinic low-risk meningioma recurrence.

作者信息

Nguyen Minh P, Morshed Ramin A, Youngblood Mark W, Perlow Haley K, Lucas Calixto-Hope G, Patel Akash J, Palmer Joshua D, Horbinski Craig M, Magill Stephen T, Chen William C, Raleigh David R

机构信息

Department of Pathology, University of California San Francisco, San Francisco, California, USA.

Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.

出版信息

Neuro Oncol. 2025 Feb 10;27(2):445-454. doi: 10.1093/neuonc/noae198.

DOI:10.1093/neuonc/noae198

PMID:39340366

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11812033/

Abstract

BACKGROUND

Despite reassuring clinical and histological features, low-grade meningiomas can recur after surgery. Targeted gene expression profiling improves risk stratification of meningiomas, but the utility of this approach for clinical low-risk meningiomas is incompletely understood.

METHODS

This was a multicenter retrospective cohort study of meningiomas from patients who were treated at 4 institutions from 1992 to 2023. Adult patients with newly diagnosed or recurrent World Health Organization (WHO) grade 1 meningiomas that were treated with gross total resection (GTR) or subtotal resection (STR), or newly diagnosed WHO grade 2 meningiomas that were treated with GTR, were included. A 34-gene expression biomarker and gene expression risk score (continuous from 0 to 1) was evaluated in all samples.

RESULTS

The study cohort was comprised of 723 patients, none of which were used for discovery or training of the gene expression biomarker and 265 of which were previously unreported. There were 626 WHO grade 1 meningiomas, 490 with GTR and 126 with STR, and 97 WHO grade 2 meningiomas with GTR. Targeted gene expression profiling classified 51.3% of clinical low-risk meningiomas as molecular intermediate-risk and 9.5% as molecular high-risk. Combining the gene expression biomarker with the extent of resection revealed that 19.8% of clinical low-risk meningiomas had unfavorable local freedom from recurrence (LFFR) and overall survival (OS), including 7.1% of newly diagnosed WHO grade 1 meningiomas with GTR. The risk score was prognostic for LFFR (HR per 0.1 increase in risk score 1.89, 95% CI: 1.58-2.25) across all WHO grades, extents of resection, and newly diagnosed or recurrent presentations.

CONCLUSIONS

Targeted gene expression profiling can identify clinical low-risk meningiomas that are likely to recur after surgery.

摘要

背景

尽管低级别脑膜瘤具有令人安心的临床和组织学特征，但手术后仍可能复发。靶向基因表达谱分析可改善脑膜瘤的风险分层，但这种方法对临床低风险脑膜瘤的效用尚未完全了解。

方法

这是一项多中心回顾性队列研究，研究对象为1992年至2023年在4家机构接受治疗的脑膜瘤患者。纳入新诊断或复发的世界卫生组织（WHO）1级脑膜瘤且接受了全切除（GTR）或次全切除（STR）的成年患者，或新诊断的接受了GTR的WHO 2级脑膜瘤患者。在所有样本中评估了一种34基因表达生物标志物和基因表达风险评分（连续范围为0至1）。

结果

研究队列包括723例患者，其中无一例用于基因表达生物标志物的发现或训练，且其中265例此前未报告。有626例WHO 1级脑膜瘤，490例接受GTR，126例接受STR，以及97例接受GTR的WHO 2级脑膜瘤。靶向基因表达谱分析将51.3%的临床低风险脑膜瘤分类为分子中风险，9.5%分类为分子高风险。将基因表达生物标志物与切除范围相结合显示，19.8%的临床低风险脑膜瘤具有不良的局部无复发生存（LFFR）和总生存期（OS），包括7.1%新诊断的接受GTR的WHO 1级脑膜瘤。风险评分对所有WHO级别、切除范围以及新诊断或复发表现的LFFR具有预后价值（风险评分每增加0.1，风险比为1.89，95%置信区间：1.58 - 2.25）。