Circulating Extracellular Vesicles as Biomarker for Diagnosis, Prognosis and Monitoring in Glioblastoma Patients

This academic paper reports a study on exosomes in patients with glioblastoma. The study explored the potential application of exosomes as biomarkers in the diagnosis, prognosis, and treatment response monitoring of glioblastoma.

EV marker changes with recurrence Academic Background: Glioblastoma is an invasive brain tumor, and despite comprehensive treatments such as surgery, chemotherapy, and radiotherapy, the overall prognosis remains poor. Patients need to undergo frequent magnetic resonance imaging (MRI) to monitor tumor recurrence, but MRI exams are expensive and challenging to interpret. Therefore, there is an urgent need to develop non-invasive and reliable methods for continuous monitoring of glioblastoma.

Exosomes are small membrane-bound vesicles secreted by cells, carrying proteins, RNA, and DNA from the source cells. Previous studies have found that the level of exosomes in the blood circulation of glioblastoma patients is significantly elevated, providing the possibility of using exosomes as biomarkers for glioblastoma.

Paper Source: This study was conducted by multiple authors, including Franz L. Ricklefs, Kathrin Wollmann, from the Department of Neurosurgery at the University Medical Center Hamburg-Eppendorf in Germany. The paper was published online in the journal Neuro-Oncology on April 3, 2024.

Research Methods and Main Results: 1. Research workflow and processing methods: The study collected plasma samples from glioblastoma patients before surgery, 1 day after surgery, and 4-6 days after surgery, as well as control samples from healthy donors. Researchers used techniques such as nanoparticle tracking analysis (NTA) and imaging flow cytometry to separate, concentrate, and quantify plasma exosomes.

  1. Key findings: (a) The concentration of exosomes in the plasma of glioblastoma patients was 5.5 times higher than that of healthy donors. (b) Patients with higher exosome concentrations had significantly shorter overall survival and progression-free survival, and exosome concentration was an independent prognostic indicator for overall survival. © Exosome concentration was related to the degree of peritumoral edema (FLAIR hyperintense signal) but not to the volume of the contrast-enhancing tumor portion, suggesting that increased blood-brain barrier permeability may be the main cause of elevated exosome levels. (d) Postoperatively, patients’ exosome concentrations rapidly decreased to normal levels, and the decrease was related to the extent of tumor resection. (e) During the stable disease period, exosome concentrations remained at normal levels; however, when the tumor recurred, exosome concentrations increased again, and in some patients, exosome levels increased even earlier than MRI detection of recurrence.

  2. Research significance: (a) Exosome concentration can serve as an independent prognostic indicator for glioblastoma patients, aiding in preoperative assessment and treatment planning. (b) Continuous monitoring of exosome concentration changes can help detect tumor recurrence at an early stage, promoting timely adjustment of treatment regimens. © The research results are expected to promote the application of exosome testing in clinical diagnosis and monitoring of glioblastoma, complementing the shortcomings of MRI examinations.

Research Highlights: 1. The plasma exosome concentration in glioblastoma patients is significantly elevated and is an independent prognostic indicator for overall survival. 2. Exosome concentration is related to peritumoral edema rather than tumor volume itself, suggesting that it mainly originates from increased blood-brain barrier permeability. 3. Postoperatively, exosome concentrations rapidly decrease, maintain normal levels during stable disease, but increase again upon recurrence, potentially earlier than imaging detection.