Elevated levels of MIC-1/GDF15 in the cerebrospinal fluid of patients are associated with glioblastoma and worse outcome

Authors

  • Sophie Shnaper,

    1. Laboratory of Brain Tumor Biology and Genetics, Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    Search for more papers by this author
  • Isabelle Desbaillets,

    1. Laboratory of Brain Tumor Biology and Genetics, Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    Search for more papers by this author
  • David A. Brown,

    1. Centre for Immunology St. Vincent's Hospital, University of South Wales, Sydney, Australia
    Search for more papers by this author
  • Anastasia Murat,

    1. Laboratory of Brain Tumor Biology and Genetics, Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    2. National Center of Competence in Research Molecular Oncology, Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Lausanne, Switzerland
    Search for more papers by this author
  • Eugenia Migliavacca,

    1. National Center of Competence in Research Molecular Oncology, Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Lausanne, Switzerland
    2. Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne, Switzerland
    Search for more papers by this author
  • Myriam Schluep,

    1. Department of Neurology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    Search for more papers by this author
  • Sandrine Ostermann,

    1. Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    Search for more papers by this author
  • Marie-France Hamou,

    1. Laboratory of Brain Tumor Biology and Genetics, Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    Search for more papers by this author
  • Roger Stupp,

    1. Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    Search for more papers by this author
  • Samuel N. Breit,

    1. Centre for Immunology St. Vincent's Hospital, University of South Wales, Sydney, Australia
    Search for more papers by this author
  • Nicolas de Tribolet,

    1. Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    2. Department of Neurosurgery, Hôpital Universitaire Genève, Geneva, Switzerland
    Search for more papers by this author
  • Monika E. Hegi

    Corresponding author
    1. Laboratory of Brain Tumor Biology and Genetics, Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
    2. National Center of Competence in Research Molecular Oncology, Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Lausanne, Switzerland
    • Laboratory of Brain Tumor Biology and Genetics, Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois (CHUV BH19-110), 46 rue du Bugnon, Lausanne 1011/Switzerland
    Search for more papers by this author
    • Fax: +41-21-314-2587.


Abstract

For patients with brain tumors identification of diagnostic and prognostic markers in easy accessible biological material, such as plasma or cerebrospinal fluid (CSF), would greatly facilitate patient management. MIC-1/GDF15 (growth differentiation factor 15) is a secreted protein of the TGF-beta superfamily and emerged as a candidate marker exhibiting increasing mRNA expression during malignant progression of glioma. Determination of MIC-1/GDF15 protein levels by ELISA in the CSF of a cohort of 94 patients with intracranial tumors including gliomas, meningioma and metastasis revealed significantly increased concentrations in glioblastoma patients (median, 229 pg/ml) when compared with control cohort of patients treated for non-neoplastic diseases (median below limit of detection of 156 pg/ml, p < 0.0001, Mann–Whitney test). However, plasma MIC-1/GDF15 levels were not elevated in the matching plasma samples from these patients. Most interestingly, patients with glioblastoma and increased CSF MIC-1/GDF15 had a shorter survival (p = 0.007, log-rank test). In conclusion, MIC-1/GDF15 protein measured in the CSF may have diagnostic and prognostic value in patients with intracranial tumors. © 2009 UICC

Ancillary