Liquid biopsy and glioblastoma

Abstract

Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on neuroimaging techniques followed by histopathological and molecular analysis of resected or biopsied tissue. A recent paradigm shift in diagnostics ranks the molecular analysis of tissue samples as the new gold standard over classical histopathology, thus correlating better with the biological behavior of glioblastoma and clinical prediction, especially when a tumor lacks the typical hallmarks for glioblastoma. Liquid biopsy aims to detect and quantify tumor-derived content, such as nucleic acids (DNA/RNA), circulating tumor cells (CTCs), or extracellular vesicles (EVs) in biofluids, mainly blood, cerebrospinal fluid (CSF), or urine. Liquid biopsy has the potential to overcome the limitations of both neuroimaging and tissue-based methods to identify early recurrence and to differentiate tumor progression from pseudoprogression, without the risks of repeated surgical biopsies. This review highlights the origins and time-frame of liquid biopsy in glioblastoma and points to recent developments, limitations, and challenges of adding liquid biopsy to support the clinical management of glioblastoma patients.

Exosomal DNA: Role in Reflecting Tumor Genetic Heterogeneity, Diagnosis, and Disease Monitoring

“…Glioblastoma, the most prevalent malignant tumor in the adult central nervous system, is characterized by increased glucose consumption and associated with a poor prognosis [ 50 , 51 , 52 ]. Due to the limited non-invasive access to the brain, the use of exoDNA for detection is of great clinical value [ 53 , 54 , 55 ]. In this study, mtDNA copy numbers and point mutations were evaluated in tissue and exoDNA samples from glioblastoma patients and a control group.…”

“…This hypothesis is supported by the discovery of mtDNA variations in Beata’s study, specifically in the mt-12S rRNA region, which can impact the oxidative capacity of the respiratory chain. However, it is important to note that further research is required to fully understand the potential of mtDNA as a reliable biomarker for glioblastoma [ 54 , 55 ]. These findings provide valuable insights into the molecular characteristics of glioblastoma and highlight the potential use of mtDNA as a biomarker for this aggressive brain tumor [ 59 ].…”

Circulating serum miR-362-3p and miR-6721-5p as potential biomarkers for classification patients with adult-type diffuse glioma

“…Collecting biofluids from patients through liquid biopsy is a minimally invasive and straightforward process. This makes diagnostics more accessible and less expensive than tissue biopsy, which is significant in terms of brain tumour ( Eibl and Schneemann, 2023 ). In recent years, miRNAs have gained importance as biomarkers for diagnosis, prognosis, and developing therapeutic strategies for breast, prostate, and lung cancers, melanoma, but also cardiovascular and neuronal diseases ( Faruq and Vecchione, 2015 ; Huang, 2017 ; Wang et al, 2018 ; Bielska et al, 2021 ).…”

Impact of hypoxia on the molecular content of glioblastoma-derived exosomes

“…Tumors such as GBM are in a constant evolutionary process and respond to clonal selection, hypoxia, and different treatment modalities. Against this background, liquid biopsy could provide a minimally invasive, safe, and highly sensitive alternative to conventional tissue biopsies for GBM patients [30] . Liquid biopsy may facilitate tumor monitoring by detecting various types of biomarkers in peripheral blood or cerebrospinal fluid, through the analysis of tumor-derived circulating material [31] .…”

“…Liquid biopsy may facilitate tumor monitoring by detecting various types of biomarkers in peripheral blood or cerebrospinal fluid, through the analysis of tumor-derived circulating material [31] . Despite advancements in liquid biopsy continuously improving its utility in the diagnosis, prognosis, and monitoring of GBM, its application remains significantly restricted [30] . This is primarily attributed to the lack of standardized techniques for sample collection and processing compared to traditional tissue biopsies, consequently leading to great variability in results and their interpretation [32] .…”