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Clinical and Translational Oncology

, Volume 20, Issue 11, pp 1439–1447 | Cite as

Prognostic and microRNA profile analysis for CD44 positive expression pediatric posterior fossa ependymoma

  • C. Shu
  • Q. Wang
  • X. Yan
  • J. Wang
Research Article
  • 190 Downloads

Abstract

Background

Ependymoma is the third most common pediatric brain tumor and occurs most frequently in the posterior fossa. However, the lack of immortalized cell lines, xenografts, or animal models has significantly hindered the study of pediatric posterior fossa ependymoma (P-PF-EPN) pathogenesis. This prompted us to use clinical big data to study this rare disease.

Methods

Application of the robust rank aggregation method revealed CD44 as a reliable biomarker in P-PF-EPN. 120 P-PF-EPN samples after surgical resection were selected for Kaplan–Merier and Cox proportion hazard regression survival analysis. Immunohistochemical analysis was performed to assess CD44 expression in the tumor samples. The miRNA profile was determined using a whole-genome miRNA microarray. The expression patterns of related mRNAs, miRNAs and proteins were validated by qRT-PCR or Western blotting.

Results

CD44 was found to be an independent predictor of prognosis in survival analysis. It improved the accuracy of using LAMA2/NELL2 for classifying P-PF-EPN molecular subgroups. Fourteen miRNAs were underexpressed, and one miRNA was overexpressed in CD44-positive P-PF-EPNs. miR-543, miR-495-3p, miR-299-3p, miR-139-5p and miR-128-3p were identified to have CD44 positively co-regulated potential target oncogenes. Two PI3K-Akt signaling pathway related potential target oncogenes (VEGFA, CSF1) for miR-299-3p and miR-495-3p were validated overexpression in CD44 positive P-PF-EPNs. Abnormal activation of the PI3K-Akt pathway was confirmed in CD44-positive cases.

Conclusions

CD44 is of great clinical significance as a prognostic biomarker. The survival difference between CD44 positive and negative P-PF-EPN is determined by a complex functional miRNA-mRNA-signaling pathway regulatory network.

Keywords

Pediatric ependymoma CD44 Survival miRNA Prognostic biomarker 

Notes

Acknowledgements

Thanks are due to the School of Medicine Nankai University for the assistance with the experiments.

Funding

The study was supported by the Foundation of Tianjin Science and Technology Committee (14JCZDJC35600) and the National Key Technology Support Program (2014BAI04B00).

Compliance with ethical standards

Conflict of interest

The authors declare that no conflicts of interest exist with regard to this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12094_2018_1876_MOESM1_ESM.docx (397 kb)
Supplementary material 1 (DOCX 396 kb)
12094_2018_1876_MOESM2_ESM.docx (57 kb)
Supplementary material 2 (DOCX 57 kb)

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.School of MedicineNankai UniversityTianjinChina
  2. 2.Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory, Tianjin Neurosurgery InstituteTianjin Huan Hu HospitalTianjinChina

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