title: Elevated levels of MIC-1/GDF15 in the cerebrospinal fluid of patients are associated with glioblastoma and worse outcome.
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.
authors.affiliation: Department of Neurosurgery, Laboratory of Brain Tumor Biology and Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Shnaper
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desbaillets
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Anastasia
authors.initials: A
authors.lastname: Murat
authors.forename: Eugenia
authors.initials: E
authors.lastname: Migliavacca
authors.forename: Myriam
authors.initials: M
authors.lastname: Schluep
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ostermann
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Hamou
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Tribolet
authors.forename: Monika E
authors.initials: ME
authors.lastname: Hegi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000134:cerebrospinal fluid*; D001932:Brain Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid* / Q000601:surgery; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000134:cerebrospinal fluid* / Q000601:surgery; D055436:Growth Differentiation Factor 15 / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D012333:RNA, Messenger