Thioredoxin system protein expression is associated with poor clinical outcome in adult and paediatric gliomas and medulloblastomas

Martin, Stewart; Yao, Anqi; Storr, Sarah J; Al-Hadyan, Khaled; Rahman, Ruman; Smith, Stuart; Grundy, Richard; Paine, Simon

Abstract

The thioredoxin (Trx) system is an important enzyme family that regulates cellular redox homeostasis. Protein expression of Trx system family members has been assessed in various cancers and linked to various clinicopathological variables, disease progression, treatment response and survival outcomes but information is lacking in brain tumours. Expression of the system was therefore examined, by immunohistochemistry in different brain tumour types, adult and paediatric cases, to determine if expression was of importance to clinical outcome. Trx system proteins were expressed, to variable levels, across all brain tumour types with significant variations in expression between different tumour types/grades/regions. High Trx reductase (TrxR) expression was linked to worse prognosis across all cohorts. High cytoplasmic TrxR expression was significantly associated with adverse overall survival (OS) in adult glioblastoma (P=0.027) and paediatric low-grade glioma (LGG) patients (P=0.012). High expression of nuclear TrxR, cytoplasmic and nuclear Trx, and Trxinteracting protein (TxNIP) was associated with improved OS in paediatric LGGs (P=0.031, P

Citation

Martin, S., Yao, A., Storr, S. J., Al-Hadyan, K., Rahman, R., Smith, S., Grundy, R., & Paine, S. (2020). Thioredoxin system protein expression is associated with poor clinical outcome in adult and paediatric gliomas and medulloblastomas. Molecular Neurobiology, 57(7), 2889–2901. https://doi.org/10.1007/s12035-020-01928-z

• Journal Article Type: Article
• Acceptance Date: May 1, 2020
• Online Publication Date: May 16, 2020
• Publication Date: May 16, 2020
• Deposit Date: May 7, 2020
• Publicly Available Date: May 19, 2020
• Journal: Molecular Neurobiology
• Print ISSN: 0893-7648
• Electronic ISSN: 1559-1182
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 57
• Issue: 7
• Pages: 2889–2901
• DOI: https://doi.org/10.1007/s12035-020-01928-z
• Keywords: Thioredoxin; Thioredoxin Reductase; glioblastoma; Low-grade glioma; High-grade glioma; Medulloblastoma
• Public URL: https://nottingham-repository.worktribe.com/output/4389172
• Publisher URL: https://link.springer.com/article/10.1007/s12035-020-01928-z