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Brain tumors are considered one of the deadliest types of cancer, being challenging to treat, especially due to the blood-brain barrier, which has been linked to treatment resistance. The genomic classification of brain tumors has been helping in the diagnostic precision, however tumor heterogeneity in addition to the difficulties to obtain tissue biopsies, represent a challenge. The biopsies are usually obtained either via neurosurgical removal or stereotactic tissue biopsy, which can be risky procedures for the patient. To overcome these challenges, liquid biopsy has become an interesting option by constituting a safer procedure than conventional biopsy, which may offer valuable cellular and molecular information representative of the whole organism. Besides, it is relatively easy to obtain such as in the case of blood (venipuncture) and urine sample collection. In the present comprehensive review, we discuss the newest information regarding liquid biopsy in the brain tumors' field, methods employed, the different sources of bio-fluids and their potential circulating targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Glioblastoma is a fatal brain tumour with a poor patient survival outcome. Hypoxia has been shown to reprogram cells towards a stem cell phenotype associated with self-renewal and drug resistance properties. Activation of hypoxia-inducible factors (HIFs) helps in cellular adaptation mechanisms under hypoxia. Similarly, miRNAs are known to be dysregulated in GBM have been shown to act as critical mediators of the hypoxic response and to regulate key processes involved in tumorigenesis., Methods: Glioblastoma (GBM) cells were exposed to oxygen deprivation to mimic a tumour microenvironment and different cell aspects were analysed such as morphological changes and gene expression of miRNAs and survival genes known to be associated with tumorigenesis., Results: It was observed that miR-128a-3p, miR-34-5p, miR-181a/b/c, were down-regulated in 6 GBM cell lines while miR-17-5p and miR-221-3p were upregulated when compared to a non-GBM control. When the same GBM cell lines were cultured under hypoxic microenvironment, a further 4-10-fold downregulation was observed for miR-34-5p, miR-128a-3p and 181a/b/c while a 3-6-fold upregulation was observed for miR-221-3p and 17-5p for most of the cells. Furthermore, there was an increased expression of SOX2 and Oct4, GLUT-1, VEGF, Bcl-2 and survivin, which are associated with a stem-like state, increased metabolism, altered angiogenesis and apoptotic escape, respectively., Conclusion: This study shows that by mimicking a tumour microenvironment, miRNAs are dysregulated, stemness factors are induced and alteration of the survival genes necessary for the cells to adapt to the micro-environmental factors occurs. Collectively, these results might contribute to GBM aggressiveness., (© 2021. The Author(s).)