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Diagnostic biomarkers from proteomic characterization of cerebrospinal fluid in patients with brain malignancies
Author(s) -
Schmid Dominic,
Warnken Uwe,
Latzer Pauline,
Hoffmann Dirk C.,
Roth Judith,
Kutschmann Stefanie,
Jaschonek Hannah,
Rübmann Petra,
Foltyn Martha,
Vollmuth Philipp,
Winkler Frank,
Seliger Corinna,
Felix Marius,
Sahm Felix,
Haas Jürgen,
Reuss David,
Bendszus Martin,
Wildemann Brigitte,
Deimling Andreas,
Wick Wolfgang,
Kessler Tobias
Publication year - 2021
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.15350
Subject(s) - cerebrospinal fluid , glioma , medicine , brain tumor , proteomics , pathology , proteome , brain metastasis , biomarker , glial fibrillary acidic protein , oncology , cancer , metastasis , bioinformatics , immunohistochemistry , cancer research , biology , gene , biochemistry
Recent technological advances in molecular diagnostics through liquid biopsies hold the promise to repetitively monitor tumor evolution and treatment response of brain malignancies without the need of invasive surgical tissue accrual. Here, we implemented a mass spectrometry‐based protein analysis pipeline which identified hundreds of proteins in 251 cerebrospinal fluid (CSF) samples from patients with four types of brain malignancies (glioblastoma, lymphoma, brain metastasis, and leptomeningeal disease [LMD]) and from healthy individuals with a focus on glioblastoma in a retrospective and confirmatory prospective observational study. CSF proteome deregulation via disruption of the blood brain barrier appeared to be largely conserved across brain tumor entities. 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 glioblastoma tumor tissue and primary glioblastoma cells, we identified potential CSF biomarkers for glioblastoma, in particular chitinase‐3‐like protein 1 (CHI3L1) and glial fibrillary acidic protein (GFAP). Key findings were validated in a prospective cohort consisting of 35 glioma patients. Finally, in LMD patients who frequently undergo repeated CSF work‐up, we explored our proteomic pipeline as a mean to profile consecutive CSF samples. Therefore, proteomic analysis of CSF in brain malignancies has the potential to reveal biomarkers for diagnosis and therapy monitoring.

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