期刊
BRAIN TUMOR PATHOLOGY
卷 38, 期 2, 页码 109-121出版社
SPRINGER JAPAN KK
DOI: 10.1007/s10014-021-00396-0
关键词
Medulloblastoma; Neuronal markers; GFAP; GLI3; TOP2β
资金
- AMED [JP18dm0107105, JP16kk0205009]
- Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labour and Welfare Sciences Research Grants, the Ministry of Health, Labour and Welfare, Japan
The study highlights the association of GLI3, NM, GFAP, and TOP2 beta expressions with prognosis in medulloblastomas, showing different clinical characteristics and outcomes among NM-/GFAP-, NM+/GFAP-, and GFAP+ subgroups.
We previously reported observing GLI3 in medulloblastomas expressing neuronal markers (NM) and/or glial fibrillary acidic protein (GFAP). Furthermore, patients with medulloblastomas expressing NM or GFAP tended to show favorable or poor prognosis, respectively. In the present study, we focused on the role of topoisomerase II beta (TOP2 beta) as a possible regulator for neuronal differentiation in medulloblastomas and examined the pathological roles of GLI3, NM, GFAP, and TOP2 beta expressions in a larger population. We divided 124 medulloblastomas into three groups (NM-/GFAP-, NM +/GFAP-, and GFAP +) based on their immunoreactivity (IR) against NM and GFAP. The relationship among GLI3, NM, GFAP, and TOP2 beta was evaluated using fluorescent immunostaining and a publicly available single-cell RNA sequencing dataset. In total, 87, 30, and 7 medulloblastomas were classified as NM-/GFAP-, NM + /GFAP-, and GFAP +, and showed intermediate, good, and poor prognoses, respectively. GLI3-IR was frequently observed in NM +/GFAP- and GFAP + , and TOP2 beta-IR was frequently observed only in NM +/GFAP- medulloblastomas. In fluorescent immunostaining, TOP2 beta-IR was mostly co-localized with NeuN-IR but not with GFAP-IR. In single-cell RNA sequencing, TOP2 beta expression was elevated in CMAS/DCX-positive, but not in GFAP-positive, cells. NM-IR and GFAP-IR are important for estimating the prognosis of patients with medulloblastoma; hence they should be assessed in clinical practice.
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