Circulating biomarkers in patients with glioblastoma

Abstract

Gliomas are the most common tumours of the central nervous system and the most aggressive form is glioblastoma (GBM). Despite advances in treatment, patient survival remains low. GBM diagnosis typically relies on imaging techniques and postoperative pathological diagnosis; however, both procedures have their inherent limitations. Imaging modalities cannot differentiate tumour progression from treatment-related changes that mimic progression, known as pseudoprogression, which might lead to misinterpretation of therapy response and delay clinical interventions. In addition to imaging limitations, tissue biopsies are invasive and most of the time cannot be performed over the course of treatment to evaluate 'real-time' tumour dynamics. In an attempt to address these limitations, liquid biopsies have been proposed in the field. Blood sampling is a minimally invasive procedure for a patient to endure and could provide tumoural information to guide therapy. Tumours shed tumoural content, such as circulating tumour cells, cell-free nucleic acids, proteins and extracellular vesicles, into the circulation, and these biomarkers are reported to cross the blood-brain barrier. The use of liquid biopsies is emerging in the field of GBM. In this review, we aim to summarise the current literature on circulating biomarkers, namely circulating tumour cells, circulating tumour DNA and extracellular vesicles as potential non-invasively sampled biomarkers to manage the treatment of patients with GBM.

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

“…Regulation of EV release is critical for cellular communication and modulation of the microenvironment in cancer progression and metastasis and recognised to be of increasing importance in GBM [21,22]. GBM-derived EVs have furthermore been shown to induce tumour-promoting transformation of subventricular zone resident neural stem cells, possibly contributing to GBM recurrence [64].…”

“…Extracellular vesicles (EVs) are recognised players in mediating such changes, being lipid bilayer-enclosed structures, 30-1000 nm in diameter, released from cells and acting as key-mediators for intra/inter-tumour communication through horizontal transfer of functional proteins and nucleic acids (mRNA, miRNA, lncRNA, sncRNA) [17][18][19][20]. EVs have great potential as diagnostic and prognostic biomarkers in a range of pathologies, including GBM, and therefore increased understanding of EV-mediated functions in GBM biology is urgently needed [21,22]. In GBM, EV protein-cargo has for example been associated with the phenotypic signature of GBM cells [23], while TMZ treatment has been shown to increase EV release in GBM and to promote more pro-oncogenic EV signatures [24].…”

A competing endogenous RNA mechanism in glioblastoma is investigated by bioinformatics analysis

“…The current treatment of GBM includes a combination of surgery, radiotherapy and chemotherapy, and the standard chemotherapy drug in use is temozolomide (TMZ). Nevertheless, on account of the high drug resistance rate to treatment and recurrence rate of GBM patients, the overall survival is poor, with only a median survival period of about 15 months (26). Hence, the novel therapeutic target and treatment strategy should be investigated.…”

Novel Molecular Markers in Glioblastoma—Benefits of Liquid Biopsy

“…Additionally, the proteomic profiling of these EVs showed a glioblastoma-specific pattern with EGFR amplifications, PTEN deletions, IDH1/2, and TP53 mutations [ 73 ]. In another study, it was found that syndecan-1 present in plasma EVs can be useful to distinguish low-grade from high-grade glioma with a sensitivity of 71% and a specificity of 80% [ 74 ]. Certain miRNAs, as it was demonstrated for example by Ebrahimkhani et al, are selectively packaged into exosomes regulating cell proliferation in glioma.…”