Gene expression analysis during progression of malignant meningioma compared to benign meningioma

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  • 1 Departments of Neurosurgery and
  • | 2 Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;
  • | 3 Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark;
  • | 4 Department of Neurosurgery, Karolinska University Hospital, Solna, Stockholm, Sweden;
  • | 5 Department of Clinical Neuroscience, Karolinska Institutet, Solna, Stockholm, Sweden;
  • | 6 Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark;
  • | 7 Department of Pathology, Danish Reference Center for Prion Diseases, Copenhagen University Hospital, Copenhagen, Denmark;
  • | 8 Department of Ophthalmology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;
  • | 9 Department of Clinical Medicine and Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark;
  • | 10 Department of Pathology, The Bartholin Institute, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;
  • | 11 Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark;
  • | 12 Departments of Neurological Surgery and
  • | 13 Radiation Oncology, University of California, San Francisco, California;
  • | 14 Department of Neurosurgery, Odense University Hospital, Odense, Denmark;
  • | 15 Clinical Institute and BRIDGE, University of Southern Denmark, Odense, Denmark; and
  • | 16 Departments of Immunology and Microbiology and
  • | 17 Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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OBJECTIVE

Meningioma is the most common primary intracranial neoplasm. Only 1%–3% of meningiomas are malignant according to the 2016 WHO criteria (WHO grade III). High-grade meningiomas present specific gene expression signatures indicating aggressive growth or recurrence. However, changes in gene expression and in neuroinflammatory gene expression signatures in WHO grade III meningiomas and during progression from WHO grade I or II to grade III are unknown.

METHODS

The authors used a NanoString targeted gene expression panel with focus on 787 genes relevant in meningioma pathology and neuroinflammatory pathways to investigate patients with grade III meningiomas treated at Rigshospitalet from 2000 to 2020 (n = 51). A temporal dimension was added to the investigation by including samples from patients’ earlier grade I and II meningiomas and grade III recurrences (n = 139 meningiomas). The authors investigated changes in neuroinflammatory gene expression signatures in 1) grade I meningiomas that later transformed into grade III meningiomas, and 2) grade III meningiomas compared with nonrecurrent grade I meningiomas.

RESULTS

The authors’ data indicate that FOXM1, TOP2A, BIRC5, and MYBL2 were enriched and the HOTAIR regulatory pathway was enriched in grade III meningiomas compared with nonrecurrent grade I meningiomas. They discovered a separation of malignant and benign meningiomas based only on genes involved in microglia regulation with enrichment of P2RY12 in grade I compared with grade III meningiomas. Interestingly, FOXM1 was upregulated in premalignant grade I meningioma years before the grade III transformation.

CONCLUSIONS

The authors found gene expression changes in low-grade meningiomas that predated histological transformation to grade III meningiomas. Neuroinflammation genes distinguished grade III from grade I meningiomas.

ABBREVIATIONS

DEG = differentially expressed gene; DV300 = percentage of RNA fragments > 300 nucleotides; PBI = probabilistic index; RIN = RNA integrity number; TAM = tumor-associated macrophage; UHCL = unsupervised hierarchical clustering.

Supplementary Materials

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