Expression analysis of stem cell-related genes reveal OCT4 as a predictor of poor clinical outcome in medulloblastoma

• Published in: Journal of neuro-oncology Vol. 106; no. 1; pp. 71 - 79
• Main Authors: Rodini, Carolina Oliveira, Suzuki, Daniela Emi, Saba-Silva, Najsla, Cappellano, Andréa, de Souza, Jorge Estefano Santana, Cavalheiro, Sérgio, Toledo, Silvia Regina Caminada, Okamoto, Oswaldo Keith
• Format: Journal Article
• Language: English
• Published: Boston Springer US 2012; Springer Nature B.V
• Subjects: AC133 Antigen; Adolescent; Antigens, CD - biosynthesis; Antigens, CD - genetics; Arnold-Chiari Malformation - genetics; Biomarkers; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Child; Child, Preschool; Clinical outcomes; Female; Gene Expression Regulation, Neoplastic - genetics; Gene Expression Regulation, Neoplastic - physiology; Glycoproteins - biosynthesis; Glycoproteins - genetics; Humans; Kaplan-Meier Estimate; Laboratory Investigation - Human/Animal Tissue; Male; Medicine; Medicine & Public Health; Medulloblastoma; Medulloblastoma - drug therapy; Medulloblastoma - genetics; Medulloblastoma - pathology; Neural stem cells; Neurology; Oct-4 protein; Octamer Transcription Factor-3 - biosynthesis; Octamer Transcription Factor-3 - genetics; Oncology; Pediatrics; Peptides - genetics; Predictive Value of Tests; Prognosis; Real-Time Polymerase Chain Reaction; Risk Assessment; Risk factors; RNA-Binding Proteins - biosynthesis; RNA-Binding Proteins - genetics; Stem Cells - physiology; Survival; Tumors; Stem cell markers; Medulloblastoma; Prognosis
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-011-0647-9

Aberrant expression of stem cell-related genes in tumors may confer more primitive and aggressive traits affecting clinical outcome. Here, we investigated expression and prognostic value of the neural stem cell marker CD133 , as well as of the pluripotency genes LIN28 and OCT4 in 37 samples of pediatric medulloblastoma, the most common and challenging type of embryonal tumor. While most medulloblastoma samples expressed CD133 and LIN28 , OCT4 expression was found to be more sporadic, with detectable levels occurring in 48% of tumors. Expression levels of OCT4 , but not CD133 or LIN28 , were significantly correlated with shorter survival ( P  ≤ 0.0001). Median survival time of patients with tumors hyperexpressing OCT4 and tumors displaying low/undetectable OCT4 expression were 6 and 153 months, respectively. More importantly, when patients were clinically stratified according to their risk of tumor recurrence, positive OCT4 expression in primary tumor specimens could discriminate patients classified as average risk but which further deceased within 5 years of diagnosis (median survival time of 28 months), a poor clinical outcome typical of high risk patients. Our findings reveal a previously unknown prognostic value for OCT4 expression status in medulloblastoma, which might be used as a further indicator of poor survival and aid postoperative treatment selection, with a particular potential benefit for clinically average risk patients.