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MiR-21 expression in the tumor cell compartment holds unfavorable prognostic value in gliomas

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Abstract

High-grade gliomas are some of the most lethal forms of human cancer, and new clinical biomarkers and therapeutic targets are highly needed. MicroRNAs (miRNAs), a group of short noncoding RNAs, hold great potential as new biomarkers and targets as they are commonly deregulated in a variety of diseases including gliomas. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in several cancers including gliomas and is therefore very promising as a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in gliomas, paraffin-embedded glioma tissue samples from 193 patients with grade I, II, III, and IV tumors were analyzed by in situ hybridization (ISH) using LNA-DNA chimeric probes. We found miR-21 expression in tumor cells and tumor-associated blood vessels, whereas no expression was seen in adjacent normal brain parenchyma. Using advanced image analysis we obtained quantitative estimates reflecting the miR-21 expression levels in each of these compartments. The miR-21 levels correlated significantly with grade [p = 0.027, r s = 0.161, 95 % confidence interval (CI), 0.015–0.301] with the highest levels measured in glioblastomas. Only tumor cell miR-21 was associated with poor prognosis when adjusting for known clinical parameters (age, grade, and sex) in a multivariate analysis [p = 0.049, hazard ratio (HR) = 1.545, 95 % CI, 1.002–2.381]. In conclusion, we have shown that miR-21 is located in both tumor cells and tumor blood vessels and that its level in the tumor cell compartment holds unfavorable prognostic value in gliomas.

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Acknowledgments

We are very grateful for the technical support and advice from Department of Biostatistics, University of Southern Denmark, Odense. The work was supported by the Region of Southern Denmark, The Research Council for Health and Disease (FSS), The grant of Else and Åge Grønbæk-Olsen, The Foundation of Merchant M. Kristian Kjær and wife Margrethe Kjær born la Cour-Holmen, The grant of fmr. Dir. Leo Nielsen and wife Karen Margrethe Nielsen for medical basic research, The Beckett Foundation, Research Foundation of University of Southern Denmark, The Foundation of Fam. Hede Nielsen, The Foundation of Margot and John Friberg, The Foundation of Dir. Jacob Madsen and wife Olga Madsen, The grant of Carl and Ellen Hertz for Danish medicine and science, and The Foundation of engineer Bent Bøgh and wife Inge Bøgh.

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  1. Boye Schnack Nielsen

    Present address: Bioneer A/S, Hørsholm, Denmark

Authors and Affiliations

  1. Department of Pathology, Odense University Hospital, Winsløwparken, 15, 3. Floor, 5000, Odense C, Denmark

    Simon Kjær Hermansen, Rikke Hedegaard Dahlrot & Bjarne Winther Kristensen

  2. Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark

    Simon Kjær Hermansen, Rikke Hedegaard Dahlrot, Steinbjørn Hansen & Bjarne Winther Kristensen

  3. Department of Oncology, Odense University Hospital, Odense C, Denmark

    Rikke Hedegaard Dahlrot & Steinbjørn Hansen

  4. Exiqon A/S, Diagnostic Product Development, Vedbæk, Denmark

    Boye Schnack Nielsen

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  1. Simon Kjær Hermansen
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Correspondence to Bjarne Winther Kristensen.

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Hermansen, S.K., Dahlrot, R.H., Nielsen, B.S. et al. MiR-21 expression in the tumor cell compartment holds unfavorable prognostic value in gliomas. J Neurooncol 111, 71–81 (2013). https://doi.org/10.1007/s11060-012-0992-3

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  • DOI: https://doi.org/10.1007/s11060-012-0992-3

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