A prognostic gene-expression signature and risk score for meningioma recurrence after resection

William C. Chen, Harish N. Vasudevan, Abrar Choudhury, Melike Pekmezci, Calixto Hope G. Lucas, Joanna Phillips, Stephen T. Magill, Matthew S. Susko, Steve E. Braunstein, Nancy Ann Oberheim Bush, Lauren Boreta, Jean L. Nakamura, Javier E. Villanueva-Meyer, Penny K. Sneed, Arie Perry, Michael W. McDermott, David A. Solomon, Philip V. Theodosopoulos, David R. Raleigh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Prognostic markers for meningioma are needed to risk-stratify patients and guide postoperative surveillance and adjuvant therapy. OBJECTIVE: To identify a prognostic gene signature for meningioma recurrence and mortality after resection using targeted gene-expression analysis. METHODS: Targeted gene-expression analysis was used to interrogate a discovery cohort of 96 meningiomas and an independent validation cohort of 56 meningiomas with comprehensive clinical follow-up data from separate institutions. Bioinformatic analysis was used to identify prognostic genes and generate a gene-signature risk score between 0 and 1 for local recurrence. RESULTS: We identified a 36-gene signature of meningioma recurrence after resection that achieved an area under the curve of 0.86 in identifying tumors at risk for adverse clinical outcomes. The gene-signature risk score compared favorably to World Health Organization (WHO) grade in stratifying cases by local freedom from recurrence (LFFR, P<.001 vs .09, log-rank test), shorter time to failure (TTF, F-test, P<.0001), and overall survival (OS, P<.0001 vs .07) and was independently associated with worse LFFR (relative risk [RR] 1.56, 95% CI 1.30-1.90) and OS (RR 1.32, 95% CI 1.07-1.64), after adjusting for clinical covariates. When tested on an independent validation cohort, the gene-signature risk score remained associated with shorter TTF (F-test, P = .002), compared favorably to WHO grade in stratifying cases by OS (P = .003 vs P = .10), and was significantly associated with worse OS (RR 1.86, 95% CI 1.19-2.88) on multivariate analysis. CONCLUSION: The prognostic meningioma gene-expression signature and risk score presented may be useful for identifying patients at risk for recurrence.

Original languageEnglish (US)
Pages (from-to)202-210
Number of pages9
JournalNeurosurgery
Volume88
Issue number1
DOIs
StatePublished - Jan 1 2021
Externally publishedYes

Keywords

  • Biomarker
  • Expression
  • Gene
  • Gene expression
  • Meningioma
  • Prognostic
  • Radiation
  • Recurrence
  • Resection
  • Survival
  • WHO grade

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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