Send to

Choose Destination
Clin Cancer Res. 2019 Jan 24. pii: clincanres.2946.2018. doi: 10.1158/1078-0432.CCR-18-2946. [Epub ahead of print]

Ultrasensitive immunoprofiling of plasma extracellular vesicles identifies syndecan-1 as a potential tool for minimally invasive diagnosis of glioma.

Author information

Section of Oncology and Pathology, Department of Clinical Sciences, Lund University.
National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Department of Medical Sciences, Uppsala University.
Oncology-Pathology, Karolinska Institutet.
Aalborg University.
Karolinska Institute.
Biomedical Engineering, Lund University.
Division of Neuropathology, Department of Genetics and Pathology, Lund University.
Clinical Sciences/Radiology, Lund University.
Section of Oncology and Pathology, Department of Clinical Sciences, Lund University



Liquid biopsy has great potential to improve the management of brain tumor patients at high risk of surgery-associated complications. Here, the aim was to explore plasma extracellular vesicle (plEV) immunoprofiling as a tool for non-invasive diagnosis of glioma.


PlEV isolation and analysis were optimized using advanced mass spectrometry, nanoparticle tracking analysis and electron microscopy. We then established a new procedure that combines size exclusion chromatography isolation and proximity extension assay (PEA)-based, ultrasensitive immunoprofiling of plEV proteins that was applied on a well-defined glioma study cohort (n=82).


Among potential candidates, we for the first time identify syndecan-1 (SDC1) as a plEV constituent that can discriminate between high grade glioblastoma multiforme (GBM, WHO grade IV) and low grade glioma (LGG, WHO grade II) (AUC: 0.81; sensitivity: 71%; specificity: 91%). These findings were independently validated by ELISA. Tumor SDC1 mRNA expression similarly discriminated between GBM and LGG in an independent glioma patient population from The Cancer Genome Atlas cohort (AUC: 0.91; sensitivity: 79%; specificity: 91%). In experimental studies with GBM cells, we show that SDC1 is efficiently sorted to secreted EVs. Importantly, we found strong support of plEVSDC1 originating from GBM tumors, as plEVSDC1 correlated with SDC1 protein expression in matched patient tumors, and plEVSDC1 was decreased post-operatively depending on extent of surgery.


Our studies support the concept of circulating plEVs as a tool for non-invasive diagnosis and monitoring of gliomas, and should move this field closer to the goal of improving the management of cancer patients.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center