期刊
JOURNAL OF NEUROCHEMISTRY
卷 158, 期 2, 页码 522-538出版社
WILEY
DOI: 10.1111/jnc.15350
关键词
cerebrospinal fluid; glioblastoma; proteomic profiling
资金
- German Cancer Research Center (DKFZ)
- NCT Heidelberg [NCT 3.0 G840]
- German Research Foundation [SFB 1389, TP A03]
Recent advancements in molecular diagnostics using liquid biopsies have shown promise in monitoring tumor evolution and treatment response for brain malignancies. A study utilizing mass spectrometry-based protein analysis of cerebrospinal fluid samples identified potential biomarkers for glioblastoma and revealed proteomic changes associated with different brain tumor entities. This approach has the potential to enhance diagnosis and therapy monitoring for brain malignancies.
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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