Elevated levels of MIC-1/GDF15 in the cerebrospinal fluid of patients are associated with glioblastoma and worse outcome.
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.
Shnaper
Sophie
S
Department of Neurosurgery, Laboratory of Brain Tumor Biology and Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Desbaillets
Isabelle
I
Brown
David A
DA
Murat
Anastasia
A
Migliavacca
Eugenia
E
Schluep
Myriam
M
Ostermann
Sandrine
S
Hamou
Marie-France
MF
Stupp
Roger
R
Breit
Samuel N
SN
de Tribolet
Nicolas
N
Hegi
Monika E
ME
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
D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D012333:RNA, Messenger