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

Int J Cancer. 2009 Dec 1;125(11):2624-30. doi: 10.1002/ijc.24639.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / cerebrospinal fluid*
  • Brain Neoplasms / blood
  • Brain Neoplasms / cerebrospinal fluid*
  • Brain Neoplasms / surgery
  • Case-Control Studies
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glioblastoma / blood
  • Glioblastoma / cerebrospinal fluid*
  • Glioblastoma / surgery
  • Growth Differentiation Factor 15 / blood
  • Growth Differentiation Factor 15 / cerebrospinal fluid*
  • Growth Differentiation Factor 15 / genetics
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • RNA, Messenger