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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2014

Open Access 01-12-2014 | Research

Microrna expression signatures predict patient progression and disease outcome in pediatric embryonal central nervous system neoplasms

Authors: Maria Braoudaki, George I Lambrou, Krinio Giannikou, Vasilis Milionis, Kalliopi Stefanaki, Diane K Birks, Neophytos Prodromou, Aggeliki Kolialexi, Antonis Kattamis, Chara A Spiliopoulou, Fotini Tzortzatou-Stathopoulou, Emmanouel Kanavakis

Published in: Journal of Hematology & Oncology | Issue 1/2014

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Abstract

Background

Although, substantial experimental evidence related to diagnosis and treatment of pediatric central nervous system (CNS) neoplasms have been demonstrated, the understanding of the etiology and pathogenesis of the disease remains scarce. Recent microRNA (miRNA)-based research reveals the involvement of miRNAs in various aspects of CNS development and proposes that they might compose key molecules underlying oncogenesis. The current study evaluated miRNA differential expression detected between pediatric embryonal brain tumors and normal controls to characterize candidate biomarkers related to diagnosis, prognosis and therapy.

Methods

Overall, 19 embryonal brain tumors; 15 Medulloblastomas (MBs) and 4 Atypical Teratoid/Rabdoid Tumors (AT/RTs) were studied. As controls, 13 samples were used; The First-Choice Human Brain Reference RNA and 12 samples from deceased children who underwent autopsy and were not present with any brain malignancy. RNA extraction was carried out using the Trizol method, whilst miRNA extraction was performed with the mirVANA miRNA isolation kit. The experimental approach included miRNA microarrays covering 1211 miRNAs. Quantitative Real-Time Polymerase Chain Reaction was performed to validate the expression profiles of miR-34a and miR-601 in all 32 samples initially screened with miRNA microarrays and in an additional independent cohort of 30 patients (21MBs and 9 AT/RTs). Moreover, meta-analyses was performed in total 27 embryonal tumor samples; 19 MBs, 8 ATRTs and 121 control samples. Twelve germinomas were also used as an independent validation cohort. All deregulated miRNAs were correlated to patients’ clinical characteristics and pathological measures.

Results

In several cases, there was a positive correlation between individual miRNA expression levels and laboratory or clinical characteristics. Based on that, miR-601 could serve as a putative tumor suppressor gene, whilst miR-34a as an oncogene. In general, miR-34a demonstrated oncogenic roles in all pediatric embryonal CNS neoplasms studied.

Conclusions

Deeper understanding of the aberrant miRNA expression in pediatric embryonal brain tumors might aid in the development of tumor-specific miRNA signatures, which could potentially afford promising biomarkers related to diagnosis, prognosis and patient targeted therapy.
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Metadata
Title
Microrna expression signatures predict patient progression and disease outcome in pediatric embryonal central nervous system neoplasms
Authors
Maria Braoudaki
George I Lambrou
Krinio Giannikou
Vasilis Milionis
Kalliopi Stefanaki
Diane K Birks
Neophytos Prodromou
Aggeliki Kolialexi
Antonis Kattamis
Chara A Spiliopoulou
Fotini Tzortzatou-Stathopoulou
Emmanouel Kanavakis
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2014
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-014-0096-y

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