MicroRNAs in Cerebrospinal Fluid as Biomarkers in Brain Tumor Patients

Česká verzia

Authors: Alena Kopková ¹; Jiří Šána ^1,2; Marek Večeřa ¹; Pavel Fadrus ³ ; Radim Lipina ⁴; Martin Smrčka ³ ; Martina Lojová ¹; Ondřej Slabý ^1,2
Authors place of work: CEITEC – Středoevropský technologický institut, Masarykova univerzita, Brno ¹; Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno ²; Neurochirurgická klinika FN Brno ³; Neurochirurgická klinika FN Ostrava ⁴
Published in the journal: Klin Onkol 2019; 32(3): 181-186
Category: Review
doi: https://doi.org/10.14735/amko2019181

Summary

Backround: Although central nervous system (CNS) tumors are not the most common cancers, their incidence rate is constantly growing. Unfortunately, this group of cancers is characterized by a very poor prognosis with a very short average patient survival. Appropriate therapy depends on early and accurate diagnosis. However, this is often limited by brain tumor localization and heterogeneity. Therefore, new diagnostic approaches and biomarkers that are robust, sensitive, specific, and also without need of invasive biopsy, are still being sought. Cerebrospinal fluid (CSF) comes into direct contact with the CNS and becomes a suitable source of biological material that could reflect actual state of CNS. Suitable molecules in this regard appear to be microRNAs (miRNAs), short non-coding RNAs, that have been already detected in CSF and whose dysregulated levels are associated with various types of brain tumors.

Purpose: Unfortunately, the methodical approaches used for CSF miRNA analysis have not been sufficiently standardized yet. For this reason, we summarize and evaluate methodical approaches which were previously used for miRNA analysis from CSF in order to find the most appropriate ones. Subsequently, we review studies focused on miRNA with potential to become biomarkers of CNS tumors in the future.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted: 3. 1. 2019

Accepted: 3. 1. 2019

Keywords:

biomarker – MicroRNAs – cerebrospinal fluid – brain tumors

Zdroje

1. de Robles P, Fiest KM, Frolkis AD et al. The worldwide incidence and prevalence of primary brain tumors: a systematic review and meta-analysis. Neuro Oncol 2015; 17 (6): 776–783. doi: 10.1093/neuonc/nou283.

2. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep 2012; 14 (1): 48–54. doi: 10.1007/s11912-011-0203-y.

3. Ahmed R, Oborski MJ, Hwang M et al. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods. Cancer Manag Res 2014; 6: 149–170. doi: 10.2147/CMAR.S54726.

4. Kopkova A, Sana J, Fadrus P et al. Cerebrospinal fluid microRNAs as diagnostic biomarkers in brain tumors. Clin Chem Lab Med 2018; 56 (6): 869–879. doi: 10.1515/cclm-2017-0958.

5. Shalaby T, Grotzer MA. Tumor-associated CSF microRNAs for the prediction and evaluation of CNS malignancies. Int J Mol Sci 2015; 16 (12): 29103–29119. doi: 10.3390/ijms161226150.

6. Shalaby T, Achini F, Grotzer MA. Targeting cerebrospinal fluid for discovery of brain cancer biomarkers. J Cancer Metastasis Treat 2016; 2: 176–187. doi: 10.20517/2394-4722.2016.12.

7. Johanson, CE, Nuncan JA, Klinge PM et al. Multiplicity of cerebrospinal fluid functions: new challenges in health and disease. Cerebrospinal Fluid Res 2008; 5: 10. doi: 10.1186/1743-8454-5-10.

8. Kelbich P, Adam P, Sobek O et al. Základní vyšetření likvoru v diagnostice postižení centrálního nervového systému. Neurol Praxi 2009; 10 (5): 285–289.

9. Jurado R, Walker HK. Cerebrospinal fluid. In: Walker HK, Hall WD, Hurst JW (eds). Clinical methods: the history, physical, and laboratory examinations. 3rd edition. Boston: Butterworths 1990.

10. Adam P, Sobek O, Doležil D et al. Speciální likvirologie: Specifické proteiny likvoru. Labor Aktuell 2009; 4: 9–12.

11. Balhuizen JC, Bots GT, Schaberg A et al. Value of cerebrospinal fluid cytology for the diagnosis of malignancies in the central nervous system. J Neurosurg 1978; 48 (5): 747–753. doi: 10.3171/jns.1978.48.5.0747.

12. Sana J, Hajduch M, Michalek J et al. MicroRNAs and glioblastoma: roles in core signalling pathways and potential clinical implications. J Cell Mol Med 2011; 15 (8): 1636–1644. doi: 10.1111/j.1582-4934.2011.01317.x.

13. Weber JA, Baxter DH, Zhang S et al. The microRNA spectrum in 12 body fluids. Clinical chemistry 2010; 56 (11): 1733–1741. doi: 10.1373/clinchem.2010.147405.

14. Baraniskin A, Kuhnhenn J, Schlegel U et al. Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood 2011; 117 (11): 3140–3146. doi: 10.1182/blood-2010-09-308684.

15. Baraniskin A, Kuhnhenn J, Schlegel U et al. Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma. Neuro Oncol 2012; 14 (1): 29–33. doi: 10.1093/neuonc/nor169.

16. Teplyuk NM, Mollenhauer B, Gabriely G et al. MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. Neuro Oncol 2012; 14 (6): 689–700. doi: 10.1093/neuonc/nos074.

17. Drusco A, Bottoni A, Lagana A et al. A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies. Oncotarget 2015; 6 (25): 20829–20839. doi: 10.18632/oncotarget.4096.

18. Grotzer M, Shalaby T, Fiaschetti G et al. Detection and quantification of extracellular microRNAs in medulloblastoma. J Cancer Metastasis Treat 2015; 1: 67–75. doi: 10.4103/2394-4722.157068.

19. Akers JC, Ramakrishnan V, Kim R et al. MiR-21 in the extracellular vesicles (EVs) of cerebrospinal fluid (CSF): a platform for glioblastoma biomarker development. PLoS One 2013; 8: e78115. doi: 10.1371/journal.pone.0078115.

20. Akers JC, Hua W, Li H et al. A cerebrospinal fluid microRNA signature as biomarker for glioblastoma. Oncotarget 2017; 8 (40): 68769–68779. doi: 10.18632/oncotarget.18332.

21. Qu K, Lin T, Pang Q et al. Extracellular miRNA-21 as a novel biomarker in glioma: evidence from meta-analysis, clinical validation and experimental investigations. Oncotarget 2016; 7 (23): 33994–34010. doi: 10.18632/oncotarget.9188.

22. Sasayama T, Nakamizo S, Nishihara M et al. Cerebrospinal fluid interleukin-10 is a useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL). Neuro Oncol 2011; 14 (3): 368–380. doi: 10.1093/neuonc/nor203.

23. Johnstone RM. Exosomes biological significance: a concise review. Blood Cells Mol Dis 2006; 36 (2): 315–321. doi: 10.1016/j.bcmd.2005.12.001.

24. Teunissen CE, Petzold A, Bennett JL et al. A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurol 2009; 73 (22): 1914–1922. doi: 10.1212/WNL.0b013e3181c47cc2.

25. Teunissen CE, Tumani H, Bennett JL et al. Consensus guidelines for CSF and blood biobanking for CNS biomarker studies. Mult Scler Int 2011; 2011: e246412. doi: 10.1155/2011/246412.

26. Burgos KL, Javaherian A, Bomprezzi R et al. Identification of extracellular miRNA in human cerebrospinal fluid by next-generation sequencing. RNA 2013; 19 (5): 712–722. doi: 10.1261/rna.036863.112.

27. McAlexander MA, Phillips MJ, Witwer KW. Comparison of methods for miRNA extraction from plasma and quantitative recovery of RNA from cerebrospinal fluid. Front Genet 2013; 4: 83. doi: 10.3389/fgene.2013.00083.

28. Kopkova A, Sana J, Fadrus P et al. MicroRNA isolation and quantification in cerebrospinal fluid: A comparative methodical study. PLoS ONE. 2018; 13 (12): e0208580. doi: 10.1371/journal.pone.0208580.

29. Yagi Y, Ohkubo T, Kawaji H et al. Next-generation sequencing-based small RNA profiling of cerebrospinal fluid exosomes. Neurosci Lett 2017; 636: 48–57. doi: 10.1016/j.neulet.2016.10.042.

30. Akers JC, Ramakrishnan V, Kim R et al. miRNA contents of cerebrospinal fluid extracellular vesicles in glioblastoma patients. J Neurooncol 2015; 123: 205–216. doi: 10.1007/s11060-015-1784-3.