Proteomic characterization of cerebrospinal fluid in patients with brain malignancies

ABSTRACT: Recent technological advances in molecular diagnostics through liquid biopsies hold the promise to monitor tumor evolution and treatment response of brain malignancies without the need of invasive surgical tissue accrual. Here, we implemented a new mass spectrometry-based protein analysis pipeline and analyzed 251 cerebrospinal fluid (CSF) samples from patients with four types of brain malignancies (glioblastoma, lymphoma, brain metastasis and meningeal disease) as well as from healthy individuals. On average, we identified 511 ± 121 proteins per CSF sample. 169 proteins were commonly deregulated in all four types of brain malignancies compared to controls. CSF analysis of glioblastoma patients identified two proteomic clusters that correlated with tumor size and patient survival. By integrating CSF data with proteomic analyses of matching glioma tumor tissue and primary glioma cells, we identified potential CSF biomarkers for glioblastoma, in particular chitinase-3-like protein 1 (CHI3L1) and glial fibrillary acidic protein (GFAP). Results were validated in a prospective cohort with 35 glioblastoma patients. Response of a patient with meningeal disease to combinatorial drug treatment was associated with a complex shift of the proteomic signature, including detection of potential drug resistance mechanisms. Therefore, proteomic analysis of CSF in brain malignancies has the potential to reveal biomarkers for diagnosis and therapy monitoring.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: Tobias Kessker  

LAB HEAD: Wolfgang Wick

PROVIDER: PXD021984 | Pride | 2021-03-25

REPOSITORIES: Pride