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discovery of CSF-derived miRNA markers, with diagnostic biomarkers discovery and implementation. Finally there are
and prognostic significance. some other limitations to the interpretation of CSF cancer
related molecules studies as biomarker. Protein/miRNA
HOW NEAR ARE WE TO USING CSF composition of CSF is dependent on patient attributes such
MOLECULAR MARKERS FOR BRAIN as age, gender, the specific site of CSF access. [40]
CANCER DIAGNOSIS IN THE CLINIC?
CONCLUSION
The promise of CSF biochemical markers Table 3, such as
proteins and miRNA, to detect and monitor brain cancer has CSF is an invaluable diagnostic window to the pathological
swept through the oncology research area in recent years state of CNS. It is easily accessible by minimally-invasive
leading to ample publications. However, most putative standard clinical methods and can provide the necessary
markers did not progress beyond their initial discovery. biological information for the diagnosis of neurological
A striking discrepancy exists between the effort directed diseases. Biochemical molecules secreted by brain cancers
toward CSF biomarker, whether it is protein or miRNA, to the CSF hold great promise as diagnostic markers
discovery and the number of markers that made it into for a wide range of brain malignancies owing to the
clinical practice. Understanding the reasons why the significant differences that have been reported between
[83]
role of these markers is not yet established in the diagnosis their expression profiles in healthy individuals and those
of CNS tumors can help accelerate the conduit between of patients. However, significant concerns remain. Despite
their discovery and clinical implementation. One of the the sizeable published number of potential diagnostic and
confounding issues that participate in the failure of potential prognostic CSF biochemical markers their reproducibility
markers to reach the clinic is the lack of reproducibility between studies is unclear, and none have been validated
between similar studies or low correlation of results. for clinical use. The reported sample size in the literature
The most significant source for such inter-laboratory is small. Most data were generated by a limited number of
discrepancies is mainly due to differences in protein/miRNA research groups using different protocols or technologies.
preparation, in the analytical methods or the use of different No universally implemented guidelines are available yet for
technologies which may bias the analysis. There are various the CSF sample collection and preparation or for protein
platforms/techniques which exist each with specific biases profiling or miRNA extraction from CSF and importantly
that can greatly influence the relative expression of certain for data analysis. It is therefore premature to make specific
molecules in the tested CSF sample and may lead to foregone recommendations for their clinical implementation. More
conclusions. No wonder there is often a low correlation of research that includes multi-institutional research and
results obtained from different platforms or even from the longitudinal studies of large patient cohorts to validate the
clinical value of putative CSF markers, as demonstrated
same labs using kits and reagents from different vendors. for the field of cancer genomics, is certainly warranted.
Yet there are no universally implemented guidelines. Hence The road from CSF biomarker discovery, validation, until
standardization of these assays including CSF handling the translation into the clinical setting could be long and
(collection, storage and preparation) is a challenge for the difficult however, the reward for patients, clinicians and
near future. Teuniseen et al. have proposed protocols for scientists could be rather significant.
[84]
the standardization of CSF collection to minimizing blood
contamination of CSF and protocols for the standardization Acknowledgments
of CSF storage to prevent sample degradation and global This project was supported by the Swiss Research
proteome changes. [40] Foundation Child and Cancer.

Another critically important consideration is that despite Financial support and sponsorship
the fact that several advanced platforms are available the Nil.
analysis of secreted proteins/miRNA in the CSF is still a
very challenging task due to technical difficulties. Often the Conflicts of interest
scientists working on CSF biomarker discovery have limited There are no conflicts of interest.
knowledge of the protein/miRNA isolation/detection new
platforms and or the analytical requirements which may REFERENCES
hamper the subsequent markers analysis.
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Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ May 18, 2016 ¦ 183