Gene Expression Changes Associated With Recurrence After Gross Total Resection of Newly Diagnosed World Health Organization Grade 1 Meningioma

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

doi:10.1227/neu.0000000000003133

Gene Expression Changes Associated With Recurrence After Gross Total Resection of Newly Diagnosed World Health Organization Grade 1 Meningioma

Neurosurgery. 2024 Aug 5. doi: 10.1227/neu.0000000000003133. Online ahead of print.

Authors

Ramin A Morshed¹, Minh P Nguyen^{1

2

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

7

8}, Akash J Patel^{9

10}, Joshua D Palmer⁵, James P Chandler⁴, Philip V Theodosopoulos¹, Stephen T Magill⁴, William C Chen², David R Raleigh^{1

2

3}

Affiliations

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

PMID: 39101743
DOI: 10.1227/neu.0000000000003133

Abstract

Background and objective: Patients who undergo gross total resection (GTR) of Central Nervous System World Health Organization (WHO) grade 1 meningioma constitute a "low-risk" group, but some low-risk meningiomas can recur despite reassuring clinical and histological features. In this study, gene expression values in newly diagnosed WHO grade 1 meningiomas that had undergone GTR were evaluated for their association with recurrence.

Methods: This was a retrospective, international, multicenter cohort study that included WHO grade 1 meningiomas that underwent GTR, as first treatment, based on postoperative magnetic resonance imaging. Normalized gene expression values from a previously validated 34-gene panel were evaluated for their association with recurrence. Kaplan-Meier, multivariable Cox proportional hazard analyses, and K-means clustering were performed to assess the association of genes of interest with recurrence and identify molecular subgroups among clinically and histologically low-risk meningiomas.

Results: In total, 442 patients with WHO grade 1 meningiomas that underwent GTR and had available gene expression profiling data were included in the study. The median follow-up was 5.0 years (interquartile range 2.6-7.7 years), local recurrence occurred in 36 patients (8.1%), 5-year local freedom from recurrence was 90.5%, and median time to recurrence was 2.9 years (range 0.5-10.7 years). Eleven genes were associated with local recurrence, including lower expression of ARID1B, ESR1, LINC02593, PGR, and TMEM30B and higher expression of CDK6, CDKN2C, CKS2, KIF20A, PGK1, and TAGLN. Of these genes, PGK1 had the largest effect size. K-means clustering based on these 11 genes distinguished 2 molecular groups of clinically and histologically low-risk meningiomas with significant differences in local freedom from recurrence (hazard ratio 2.5, 95% CI 1.2-5.1, P = .016).

Conclusion: Gene expression profiling may help to identify newly diagnosed WHO grade 1 meningiomas that have an elevated risk of recurrence despite GTR.

Grants and funding

R01 CA262311 and P50 CA097257/Foundation for the National Institutes of Health