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Circulating serum oncologic miRNA in pediatric juvenile pilocytic astrocytoma patients predicts mural nodule volume

  • Original Article - Brain Tumors
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Abstract

Background

Juvenile pilocytic astrocytomas represent the largest group of pediatric brain tumors. The ideal management for these tumors is early, total surgical resection. To detect and track treatment response, a screening tool is needed to identify patients for surgical evaluation and assess the quality of treatment. The identification of aberrant miRNA profiles in the sera of juvenile pilocytic astrocytoma patients could provide such a screening tool.

Methods

The authors reviewed the serum profiles of 84 oncologically relevant miRNAs in pediatric juvenile pilocytic astrocytoma patients via qPCR screening.

Results

miR-21, miR-15b, miR-23a, and miR-146b were significantly elevated in the sera of JPA patients as compared to non-oncologic controls, oncologic controls, and post-JPA resection samples (p < 0.001, 0.022, 0.034, 0.044). miR-21 had the highest AUC on ROC analysis (AUC > 0.99, sensitivity 75%, specificity 100%). All four miRNAs also correlated well with tumor mural nodule size, though they only poorly correlated with total tumor size, including cystic components (Spearman’s R2: miR-21 91.7 vs 6.9%, miR-15b 86.3 vs 23.1%, miR-23a 85.8 vs 23.0%, miR-146b 59.8 vs 11.9%).

Conclusion

In this small pilot study, pediatric juvenile pilocytic astrocytoma patients had significant elevations in serum miR-21, miR-15b, miR-23a, and miR-146b levels that do not appear to be driven by hydrocephalus or local distortion of the intracranial contents. These alterations correlate with solid tumor component volume and reverse with complete tumor resection, suggesting that this serum miRNA profile may delineate biomarkers for screening and tracking juvenile pilocytic astrocytoma patients. Additional studies, with a larger cohort, are needed to verify these results.

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Acknowledgments

The authors would also like to thank Paul Kanev, MD, Jon Martin, MD, and Petronella Stoltz, APRN of the Connecticut Children’s Medical Center Division of Neurosurgery for their participation in screening and accruing patients. We would also like to thank Todd Jensen, MS for his technical assistance with specimen processing.

Funding

The Connecticut Brain Tumor Alliance and the Somberg Family provided financial support in the form of generous gifts in support of pediatric brain cancer research.

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Authors and Affiliations

  1. Division of Neurosurgery, Connecticut Children’s Medical Center, 282 Washington St, Hartford, CT, 06106, USA

    Markus Bookland & Min Tang-Schomer

  2. Department of Surgery, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT, 06032, USA

    Markus Bookland, Min Tang-Schomer & Antonina Kolmakova

  3. The Jackson Laboratory, 299 Farmington Ave, Farmington, 06032, CT, USA

    Min Tang-Schomer

  4. Division of Hematology-Oncology, Connecticut Children’s Medical Center, 282 Washington St, Hartford, CT, 06106, USA

    Eileen Gillan

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  1. Markus Bookland
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  2. Min Tang-Schomer
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Correspondence to Markus Bookland.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Connecticut Children’s Medical Center Institutional Review Board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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In this study, the authors screen a small number of patients with juvenile pilocytic astrocytoma for a range of miRNAs in their serum using a commercially available qPCR screening tool. Out of a total of 84 oncologically relevant miRNAs, they identify four that are present in the serum at a statistically higher level in patients than in controls with no disease or in patients with ependymoma. They demonstrate that the serum levels fall after resection of the tumour; in one tumour where resection was incomplete, residual miR-21 was present in the serum after surgery. The authors also demonstrate that the volume of the nodule is proportional to the level of these miRNAs in the serum. They suggest that these miRNAs would be useful to screen for pilocytic astrocytomas, to track patients on treatment, and to help distinguish these tumours from other lesions on imaging.This is an important study and builds on recent work seeking to define the role of circulating tumor markers such as cell-free DNA and RNA. Although the patient population studied is small, it forms the basis for more definitive investigation based on larger numbers of patients and controls.

This is an important study and builds on recent work seeking to define the role of circulating tumor markers such as cell-free DNA and RNA. Although the patient population studied is small, it forms the basis for more definitive investigation based on larger numbers of patients and controls.

Kristian Aquilina

London, UK

This article is part of the Topical Collection on Brain Tumours

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Bookland, M., Tang-Schomer, M., Gillan, E. et al. Circulating serum oncologic miRNA in pediatric juvenile pilocytic astrocytoma patients predicts mural nodule volume. Acta Neurochir 160, 1571–1581 (2018). https://doi.org/10.1007/s00701-018-3589-6

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  • DOI: https://doi.org/10.1007/s00701-018-3589-6

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