Autor:innen:
K. Reiners (Bonn, DE)
T. Tzaridis (La Jolla, US)
J. Weller (Bonn, DE)
D. Bachurski (Cologne, DE)
F. Shakeri (Bonn, DE)
C. Schaub (Bonn, DE)
P. Hau (Regensburg, DE)
A. Buness (Bonn, DE)
U. Schlegel (Zurich, CH)
J. Steinbach (Frankfurt, DE)
C. Seidel (Leipzig, DE)
R. Goldbrunner (Cologne, DE)
N. Schaefer (Bonn, DE)
B. Scheffler (Essen, DE)
M. Glas (Essen, DE)
L. Haeberle (Erlangen-Nuremberg, DE)
U. Herrlinger (Bonn, DE)
C. Coch (Bonn, DE)
G. Hartmann (Bonn, DE)
BACKGROUND
Detection of tumor progression in glioblastoma patients remains a major challenge. Extracellular vesicles (EVs) are potential biomarkers and can be detected in the blood of tumor patients. In this study, we evaluated the potential of serum-derived EVs from glio-blastoma patients to serve as a marker for tumor progression.
METHODS
EVs from serum of GB patients and healthy volunteers were separated by size ex-clusion chromatography and ultracentrifugation. EVs were characterized by multiple methods in accordance with MISEV2018. (EV Track ID: EV200097). Putative glioblastoma EV markers were defined by using a proximity-extension assay and bead-based flow cytometry. Tumor progression was defined according to modified RANO criteria.
RESULTS
EVs from the serum of glioblastoma patients (n = 67) showed an upregulation of CD29 (p = 0.08), CD44 (p < 0.0001), CD81 (p < 0.0001), CD146 (p < 0.0001), C1QA (p = 0.003), and histone H3 (p < 0.0001) as compared to serum EVs from healthy volunteers. For two independent cohorts of glioblastoma patients, we noted significant upregulation of C1QA, CD44, and histone H3 upon tumor progression, but not in patients with stable disease. In a multivariable logistic regression analysis, a combination of CD29, CD44, CD81, C1QA, and histone H3 correlated with RANO-defined tumor progression with an AUC of 0.76.
CONCLUSION
Measurement of CD29, CD44, CD81, C1QA, and histone H3 in serum-derived EVs of glioblastoma patients, along with standard MRI assessment, could improve detection of true tumor progression and thus be a useful tool for clinical decision making.