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

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

doi:10.1093/neuonc/noae198

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

Neuro Oncol. 2024 Sep 28:noae198. doi: 10.1093/neuonc/noae198. Online ahead of print.

Authors

Minh P Nguyen^{1

2

3}, Ramin A Morshed², Mark W Youngblood⁴, Haley K Perlow⁵, Calixto-Hope G Lucas^{6

7

8}, Akash J Patel^{9

10}, Joshua D Palmer⁵, Craig M Horbinski^{4

11}, Stephen T Magill⁴, William C Chen¹, David R Raleigh^{1

2

3}

Affiliations

¹ Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
² Department of Neurological Surgery, University of California San Francisco, San Francisco, CA.
³ Department of Pathology, University of California San Francisco, San Francisco, CA.
⁴ Department of Neurological Surgery, Northwestern University, Chicago, IL.
⁵ Department of Radiation Oncology, Ohio State University, Columbus, OH.
⁶ Department of Pathology, Johns Hopkins University, Baltimore, MD.
⁷ Department of Neurosurgery, Johns Hopkins University, Baltimore, MD.
⁸ Department of Oncology, Johns Hopkins University, Baltimore, MD.
⁹ Department of Neurosurgery, Baylor College of Medicine, Houston, TX.
¹⁰ Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX.
¹¹ The Department of Pathology, Northwestern University, Chicago, IL.

PMID: 39340366
DOI: 10.1093/neuonc/noae198

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 extent of resection revealed 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.

Keywords: Meningioma; biomarker; brain tumor; gene expression.

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