Novel Gene Expression Model for Outcome Prediction in Paediatric Medulloblastoma

• Published in: Journal of molecular neuroscience Vol. 51; no. 2; pp. 371 - 379
• Main Authors: Zakrzewska, Magdalena, Grešner, Sylwia M., Zakrzewski, Krzysztof, Zalewska-Szewczyk, Beata, Liberski, Pawel P.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2013; Springer Nature B.V
• Subjects: AC133 Antigen; Adolescent; Antigens, CD - genetics; Antigens, CD - metabolism; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biomarkers; Biomedical and Life Sciences; Biomedicine; Brain cancer; Brain research; Cell Biology; Chemotherapy; Child; Child, Preschool; Disease; Female; Fucosyltransferases - genetics; Fucosyltransferases - metabolism; Gene expression; Glycoproteins - genetics; Glycoproteins - metabolism; Humans; Infant; Lewis X Antigen - genetics; Lewis X Antigen - metabolism; Male; Medulloblastoma - diagnosis; Medulloblastoma - genetics; Medulloblastoma - metabolism; Neoplasms, Germ Cell and Embryonal - diagnosis; Neoplasms, Germ Cell and Embryonal - genetics; Neoplasms, Germ Cell and Embryonal - metabolism; Neoplastic Stem Cells - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system; Neurochemistry; Neurology; Neuropathology; Neurosciences; Neurosurgery; Oncology; Otx Transcription Factors - genetics; Otx Transcription Factors - metabolism; Pediatrics; Peptides - genetics; Peptides - metabolism; Prognosis; Proteomics; Receptors, Nerve Growth Factor - genetics; Receptors, Nerve Growth Factor - metabolism; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Stem cells; Survival analysis; Transcription, Genetic; Tumors; Poland; Children; Gene expression; Medulloblastoma; Outcome; Tumour-initiating cell
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1007/s12031-013-0016-6

Medulloblastoma is the most frequent type of embryonal tumour in the paediatric population. The disease progression in patients with this tumour may be connected with the presence of stem/tumour-initiating cells, but the precise source and characteristics of such cells is still a subject of debate. Thus, we tried to analyse biomarkers for which a connection with the presence of stem/tumour-initiating cells was suggested. We evaluated the transcriptional level of the ATOH1 , FUT4 , NGFR , OTX1 , OTX2 , PROM1 and SOX1 genes in 48 samples of medulloblastoma and analysed their usefulness in the prediction of disease outcome. The analyses showed a strong correlation of PROM1 , ATOH1 and OTX1 gene expression levels with the outcome ( p  ≤ 0.2). On the basis of the multivariate Cox regression analysis, we propose a three-gene model predicting risk of the disease, calculated as follows: . Survival analysis revealed a better outcome among standard-risk patients, with a 5-year survival rate of 65 %, compared to the 40 % rate observed among high-risk patients. The most promising advantage of such molecular analysis consists in the identification of molecular markers influencing clinical behaviour, which may in turn be useful in therapy optimization.