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Tumor Biology

, Volume 37, Issue 7, pp 9887–9897 | Cite as

miR-15a and miR-24-1 as putative prognostic microRNA signatures for pediatric pilocytic astrocytomas and ependymomas

  • M. Braoudaki
  • G. I. Lambrou
  • K. Giannikou
  • S. A. Papadodima
  • A. Lykoudi
  • K. Stefanaki
  • G. Sfakianos
  • A. Kolialexi
  • F. Tzortzatou-Stathopoulou
  • M. Tzetis
  • S. Kitsiou-Tzeli
  • E. Kanavakis
Original Article

Abstract

In the current setting, we attempted to verify and validate miRNA candidates relevant to pediatric primary brain tumor progression and outcome, in order to provide data regarding the identification of novel prognostic biomarkers. Overall, 26 resected brain tumors were studied from children diagnosed with pilocytic astrocytomas (PAs) (n = 19) and ependymomas (EPs) (n = 7). As controls, deceased children who underwent autopsy and were not present with any brain malignancy were used. The experimental approach included microarrays covering 1211 miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression profiles of miR-15a and miR-24-1. The multiparameter analyses were performed with MATLAB. Matching differentially expressed miRNAs were detected in both PAs and EPs, following distinct comparisons with the control cohort; however, in several cases, they exhibited tissue-specific expression profiles. On correlations between miRNA expression and EP progression or outcome, miR-15a and miR-24-1 were found upregulated in EP relapsed and EP deceased cases when compared to EP clinical remission cases and EP survivors, respectively. Taken together, following several distinct associations between miRNA expression and diverse clinical parameters, the current study repeatedly highlighted miR-15a and miR-24-1 as candidate oncogenic molecules associated with inferior prognosis in children diagnosed with ependymoma.

Keywords

Pilocytic astrocytomas Ependymomas MicroRNA microarrays Prognosis Biomarkers 

Abbreviations

AUC

Area under the curve

CNS

Central nervous system

DE

Differentially expressed

EPs

Ependymomas

MiRNAs

MicroRNAs

PAs

Pilocytic astrocytomas

qRT-PCR

Quantitative real-time polymerase chain reaction

ROC

Receiver operating characteristic curves

WHO

World Health Organization

Notes

Authors’ contributions

MB conceived and designed the study, performed all experiments, evaluated and interpreted data analyses, and drafted the manuscript. GIL performed all data analyses and participated in interpretation of data analyses and in drafting the manuscript. GK assisted in microarrays performance. SAP performed resections of the postmortem specimens. AL performed qRT-PCR experiments. KS performed tumor diagnosis. GS performed all tumor resections. FTS treated patients. AK, FTS, MT, KTS, and EK participated in the coordination and supervision of the study. All authors approved the final manuscript.

Compliance with ethical standards

Conflict of interests

The authors declare no competing financial or nonfinancial interests.

Supplementary material

13277_2016_4903_MOESM1_ESM.xlsx (107 kb)
Supplementary Table 1 miRNA functional annotation. Predictions of miRNA targets and pathway participation(XLSX 107 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • M. Braoudaki
    • 1
    • 2
    • 3
  • G. I. Lambrou
    • 1
  • K. Giannikou
    • 2
  • S. A. Papadodima
    • 4
  • A. Lykoudi
    • 3
  • K. Stefanaki
    • 5
  • G. Sfakianos
    • 6
  • A. Kolialexi
    • 3
  • F. Tzortzatou-Stathopoulou
    • 1
  • M. Tzetis
    • 3
  • S. Kitsiou-Tzeli
    • 3
  • E. Kanavakis
    • 2
  1. 1.First Department of PediatricsNational and Kapodistrian University of Athens, Choremeio Research Laboratory, “Aghia Sophia” Children’s HospitalAthensGreece
  2. 2.University Research Institute for the Study and Treatment of Childhood Genetic and Malignant DiseasesNational and Kapodistrian University of Athens, “Aghia Sophia” Children’s HospitalAthensGreece
  3. 3.Department of Medical GeneticsNational and Kapodistrian University of AthensAthensGreece
  4. 4.Department of Forensic Medicine and Toxicology, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  5. 5.Department of PathologyChildren’s Hospital “Aghia Sophia”AthensGreece
  6. 6.Department of NeurosurgeryChildren’s Hospital “Aghia Sophia”AthensGreece

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