Gene expression analysis during progression of malignant meningioma compared to benign meningioma.
Gene expression analysis during progression of malignant meningioma compared to benign meningioma.
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DOI：
10.3171/2022.7.jns22585
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发表时间：
2023-05-01
影响因子：
4.1
通讯作者：
Mathiesen, Tiit
中科院分区：
文献类型：
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作者：
Maier, Andrea D.;Meddis, Alessandra;Mirian, Christian;Haslund-Vinding, Jeppe;Bartek Jr, Jiri;Krog, Sebastian M.;Nguyen, Thi Uyen Phuong;Areskeviciute, Ausrine;Melchior, Linea C.;Heegaard, Steffen;Kristensen, Bjarne W.;Munch, Tina N.;Fugleholm, Kare;Ziebell, Morten;Raleigh, David R.;Poulsen, Frantz R.;Gerds, Thomas A.;Litman, Thomas;Scheie, David;Mathiesen, Tiit
脑膜瘤是最常见的原发性颅内肿瘤。根据2016年WHO标准（WHO III级），只有1%-3%的脑膜瘤是恶性的。高级别脑膜瘤存在特异性基因表达特征，提示侵袭性生长或复发。然而，WHO III级脑膜瘤和从WHO I级或II级进展到III级期间基因表达和神经炎性基因表达特征的变化尚不清楚。作者使用NanoString靶向基因表达面板，重点关注脑膜瘤病理学和神经炎症通路相关的787个基因，以研究2000年至2020年在Rigshospitalet治疗的III级脑膜瘤患者（n = 51）。通过包括患者早期I级和II级脑膜瘤和III级复发的样本（n = 139个脑膜瘤），将时间维度添加到调查中。作者研究了1）I级脑膜瘤后来转化为III级脑膜瘤和2）III级脑膜瘤与非复发I级脑膜瘤相比的神经炎性基因表达特征的变化。作者的数据表明，与非复发性I级脑膜瘤相比，FOXM 1、TOP 2A、BIRC 5和MYBL 2在III级脑膜瘤中富集，HOTAIR调节通路在III级脑膜瘤中富集。他们发现恶性和良性脑膜瘤的分离仅基于参与小胶质细胞调节的基因，与III级脑膜瘤相比，I级脑膜瘤中P2 RY 12富集。有趣的是，FOXM 1在癌前I级脑膜瘤中在III级转化前数年上调。作者发现，在组织学转化为III级脑膜瘤之前，低级别脑膜瘤的基因表达发生了变化。神经炎症基因区分III级脑膜瘤和I级脑膜瘤。
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. 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. 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. 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.