EM-010, Gene expression profiling of pediatric ependymomas from the posterior fossa reveals key differences with adult ependymomas

Lourdusamy, Anbarasu; Rogers, Hazel; Rahman, Ruman; Ward, Jennifer; Grundy, Richard

Abstract

BACKGROUND: Ependymoma in children and adults show distinct pathogenesis, biology, and clinical features, it is important to elucidate the transcriptional features that distinguish pediatric ependymomas from adults arising in same anatomical region. METHODS: Three independent gene expression datasets comprising tumor samples from posterior fossa of 126 individuals ranging from 0.4 to 63 years of age were examined using meta-analysis. The change in gene expression between pediatric (age < 18) and adult ependymoma was calculated and integrated with random-effects model. The association of gene expression and progression-free survival was analyzed using the Cox proportional hazard model. RESULTS: Using gene expression meta-analysis, we detected 751 genes that exhibit significant differential expression in pediatric ependymomas compared to adults (adjusted P-value, FDR < 0.05). Among the 751 genes, 282 were associated with the progression-free survival (FDR < 0.05, log-rank test). Of these 282 genes, 179 (including ASPM, COL4A2, ERBB4, GJC1, HES4, LAMB1, MMP9, MOXD1, TGFB1, TKTL1, VEGFA) were highly expressed in pediatric ependymomas and enriched for genes involved in angiogenesis, extracellular matrix organization, cell adhesion, division, proliferation, and differentiation, Integrin, MAPK, and VEGF signaling pathways. On the contrary, no distinct gene ontology terms and pathways were significantly enriched among the remaining 103 genes (including AGBL2, GRIA1, NELL2) that are over-expressed in adult ependymomas. In addition, higher gene expression levels in pediatric patients were associated with poor survival (ASPM: hazard ratio (HR) 2.56, 95% CI 1.49-4.40, P = 7.71 x 10−5; VEGF: 3.73, 1.68-8.26, P = 2.54 x 10−4) whereas high gene expression levels in adults were associated with good survival (NELL2: 0.53, 0.35-0.80, P = 2.4 x 10−4). Age at diagnosis, gender and age groups (pediatric and adults) were not significantly associated with survival. CONCLUSION: Our results showed a substantial difference in gene expression patterns underlying pediatric and adult ependymomas from posterior fossa.

Citation

Lourdusamy, A., Rogers, H., Rahman, R., Ward, J., & Grundy, R. EM-010, Gene expression profiling of pediatric ependymomas from the posterior fossa reveals key differences with adult ependymomas

• Presentation Conference Type: Conference Abstract
• Acceptance Date: Mar 3, 2014
• Publication Date: Jun 1, 2014
• Deposit Date: Sep 21, 2018
• Print ISSN: 1522-8517
• Electronic ISSN: 1523-5866
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Issue: Suppl_1
• Pages: i19
• Public URL: https://nottingham-repository.worktribe.com/output/1117996
• Publisher URL: https://academic.oup.com/neuro-oncology/article/16/suppl_1/i17/1064571#19159162
• PMID: 00033792