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miRNA-26a expression influences the therapy response to carmustine wafer implantation in patients with glioblastoma multiforme

  • Christoph SipplEmail author
  • Ralf Ketter
  • Luisa Braun
  • Fritz Teping
  • Louisa Schoeneberger
  • Yoo Jin Kim
  • Markus List
  • Arjang Nakhoda
  • Silke Wemmert
  • Joachim Oertel
  • Steffi Urbschat
Original Article - Tumor - Glioma
Part of the following topical collections:
  1. Tumor – Glioma

Abstract

Background

Glioblastoma multiforme is the most frequent malignant brain tumor in adults being marked with a very poor prognosis. Therapy concept implies concomitant radio-chemotherapy and facultative implantation of carmustine-eluted wafer. Current literature suggests microRNA 26a expression in glioblastoma to interact with alkylating chemotherapy. Subsequently, the aim of this study was to investigate the correlation of miRNA-26a expression and carmustine wafer implantation and its potential usefulness as a predictive marker for therapy response.

Methods

In total, 229 patients with glioblastoma multiforme were included into the final analysis. Of them, 80 cases were recruited from the Saarland University Medical Center for a retrospective matched-pair analysis stratified after therapy regime: One group (carmustine wafer group; n=40) received concomitant radio-chemotherapy with carmustine wafer implantation. The other group (control group; n=40) only received concomitant radio-chemotherapy. The results were confirmed by comparing them with an independent dataset of 149 patients from the TCGA database. All tumor specimens were evaluated for miRNA-26a expression, MGMT promoter methylation, and IDH1 R132H mutation status, and the results were correlated with the clinical data.

Results

Twenty-three patients in the carmustine wafer group showed low expression of miRNA-26a, while 17 patients showed a high expression. In the control group, 28 patients showed low expression, while 12 patients showed a high expression. The patients with high miRNA-26a expression in the carmustine wafer group were characterized by a significantly longer overall (hazard ratio [HR] 2.750 [95% CI 1.352–5.593]; p=0.004) and progression-free survival (HR 3.091 [95% CI 1.436–6.657]; p=0.003) than patients with low miRNA-26a expression. The 17 patients in the carmustine wafer group with high miRNA-26a expression showed a significantly longer progression-free survival (p=0.013) and overall survival (p=0.007) compared with the control group. There were no such correlations identified within the control group. TCGA datasets supported these findings.

Conclusions

MiRNA-26a expression turned out to be a promising predictor of therapy response and clinical outcome in glioblastoma patients treated with carmustine wafer implantation. For evaluation of the role of miRNA-26a in a combined therapy setting, further studies are needed in order to translate general findings to the patient’s individual situation.

Keywords

miRNA-26a Carmustine wafer Epigenetic Glioblastoma 

Abbreviations

CI

Confidence interval

FC

Fold change

GBM

Glioblastoma multiforme

GTR

Gross total resection

HR

Hazard ratio

KPS

Karnofsky Performance Score

MGMT

O6-Methylguanine-DNA methyltransferase

miRNA

MicroRNA

MRI

Magnetic resonance imaging

MS-PCR

Methylation-specific polymerase chain reaction

OS

Overall survival

PFS

Progression-free survival

qRT-PCR

Quantitative reverse-transcription polymerase chain reaction

STR

Subtotal resection

TCGA

The Cancer Genome Atlas

TMZ

Temozolomide

Notes

Acknowledgements

The authors wish to thank Lisa Senger for her editorial support and Sigrid Welsch for their technical assistance in miRNA and methylation analysis.

Funding information

This study was financed by Archimedes Pharma (L204150209).

Compliance with ethical standards

All procedures performed in this study were in accordance with the ethical standards of the 1964 Helsinki declaration. This article does not contain any studies with animals performed by any of the authors.

Ethics approval and consent to participate

This study was approved by the local German ethical board (Ethikkommission der Ärztekammer des Saarlandes, Saarbrücken, Germany).

Consent for publication

Written informed consent was obtained from all patients (General Medical Council of the State of Saarland, NO 93/16).

Competing interests

The authors declare that they have no competing interests.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Christoph Sippl
    • 1
    Email author
  • Ralf Ketter
    • 1
  • Luisa Braun
    • 1
  • Fritz Teping
    • 1
  • Louisa Schoeneberger
    • 1
  • Yoo Jin Kim
    • 2
  • Markus List
    • 3
  • Arjang Nakhoda
    • 1
  • Silke Wemmert
    • 4
  • Joachim Oertel
    • 1
  • Steffi Urbschat
    • 1
  1. 1.Department of Neurosurgery, Faculty of MedicineSaarland UniversityHomburg/SaarGermany
  2. 2.Institute of PathologyKaiserslauternGermany
  3. 3.Max-Planck-Institute of InformaticsSaarbrückenGermany
  4. 4.Department of Otorhinolaryngology, Faculty of MedicineSaarland UniversityHomburg/SaarGermany

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