Circulating tumour DNA, microRNA and metabolites in cerebrospinal fluid as biomarkers for central nervous system malignancies

J Clin Pathol. 2019 Apr;72(4):271-280. doi: 10.1136/jclinpath-2018-205414. Epub 2018 Nov 22.

Abstract

Central nervous system (CNS) malignancies can be difficult to diagnose and many do not respond satisfactorily to existing therapies. Monitoring patients with CNS malignancies for treatment response and tumour recurrence can be challenging because of the difficulty and risks of brain biopsies, and the low specificity and sensitivity of the less invasive methodologies that are currently available. Uncertainty about tumour diagnosis or whether a tumour has responded to treatment or has recurred can cause delays in therapeutic decisions that can impact patient outcome. Therefore, there is an urgent need to develop and validate reliable and minimally invasive biomarkers for CNS tumours that can be used alone or in combination with current clinical practices. Blood-based biomarkers can be informative in the diagnosis and monitoring of various types of cancer. However, blood-based biomarkers have proven suboptimal for analysis of CNS tumours. In contrast, circulating biomarkers in cerebrospinal fluid (CSF), including circulating tumour DNA, microRNAs and metabolites, hold promise for accurate and minimally invasive assessment of CNS tumours. This review summarises the current understanding of these three types of CSF biomarkers and their potential use in neuro-oncologic clinical practice.

Keywords: brain tumours; central nerve system; csf biochemistry; metabolism; tumour markers.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / cerebrospinal fluid*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Central Nervous System Neoplasms / cerebrospinal fluid*
  • Central Nervous System Neoplasms / genetics
  • Central Nervous System Neoplasms / metabolism
  • Central Nervous System Neoplasms / pathology
  • Circulating MicroRNA / cerebrospinal fluid*
  • Circulating MicroRNA / genetics
  • Circulating Tumor DNA / cerebrospinal fluid*
  • Circulating Tumor DNA / genetics
  • Energy Metabolism
  • Humans
  • Inflammation Mediators / cerebrospinal fluid
  • Metabolomics / methods
  • Molecular Diagnostic Techniques
  • Predictive Value of Tests
  • Prognosis
  • Reproducibility of Results

Substances

  • Biomarkers, Tumor
  • Circulating MicroRNA
  • Circulating Tumor DNA
  • Inflammation Mediators