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Circulating biomarkers for gliomas

Nature Reviews Neurology volume 11, pages 556–566 (2015)Cite this article

Subjects

Key Points

  • Biomarkers from gliomas can be detected in the blood and cerebrospinal fluid

  • Known mutations, such as the epidermal growth factor receptor variant III (EGFRvIII), can be detected by analysing soluble, circulating proteins or circulating tumour DNA

  • MicroRNAs—which are relevant as tumour regulators—can be found in extracellular vesicles (EVs) shed by the tumour cells

  • Circulating tumour cells are too scarce to enter routine clinical use as biomarkers to monitor response to therapy

  • Tumour heterogeneity, which is particularly pronounced in glioblastoma, calls for a strategy comprising multiple biomarker molecules; EVs contain several biomarker types, making them an appealing candidate for a comprehensive biomarker

  • Emerging immuno-oncological therapies have created a need for immunological biomarkers

Abstract

Currently, gliomas are diagnosed by neuroimaging, and refined diagnosis requires resection or biopsy to obtain tumour tissue for histopathological classification and grading. Blood-derived biomarkers, therefore, would be useful as minimally invasive markers that could support diagnosis and enable monitoring of tumour growth and response to treatment. Such circulating biomarkers could distinguish true progression from therapy-associated changes such as radiation necrosis, and help evaluate the persistence or disappearance of a therapeutic target, such as an oncoprotein or a targetable gene mutation, after targeted therapy. Unlike for other tumours, circulating biomarkers for gliomas are still being defined and are not yet in use in clinical practice. Circulating tumour DNA (ctDNA) isolated from plasma has been shown to reflect the mutational status of glioblastoma, and extracellular vesicles (EVs) containing ctDNA, microRNA and proteins function as rapidly adapting reservoirs for glioma biomarkers such as typical DNA mutations, regulatory microRNAs and oncoproteins. Ideally, circulating tumour cells could enable profiling of the whole-tumour genome, but they are difficult to detect and can reflect only a single cell type of the heterogeneous tumour composition, whereas EVs reflect the complex heterogeneity of the whole tumour, as well as its adaptations to therapy. Although all categories of potential blood-derived biomarkers need to be developed further, findings from other tumour types suggest that EVs are the most promising biomarkers.

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Figure 1: Gliomas—genetic landscape and biomarkers.
Figure 2: The origin of circulating biomarkers for gliomas.

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Acknowledgements

Neuro-oncology research in the Department of Neurosurgery, University Hospital Eppendorf has been supported by the Deutsche Forschungsgemeinschaft (LA1300), the Deutsche Krebshilfe, the Roggenbuck Stiftung, Hamburg and the Rickertsen Stiftung, Hamburg.

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  1. Department of Neurosurgery, University Hospital Eppendorf, Martinistrasse 52, Hamburg, 20246, Germany

    Manfred Westphal

  2. Laboratory for Brain Tumor Biology, University Hospital Eppendorf, Martinistrasse 52, Hamburg, 20246, Germany

    Katrin Lamszus

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Correspondence to Manfred Westphal.

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Westphal, M., Lamszus, K. Circulating biomarkers for gliomas. Nat Rev Neurol 11, 556–566 (2015). https://doi.org/10.1038/nrneurol.2015.171

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