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Ultrasensitive Immunoprofiling of Plasma Extracellular Vesicles Identifies Syndecan-1 as a Potential Tool for Minimally Invasive Diagnosis of Glioma
Lund Univ, Sect Oncol & Pathol, Dept Clin Sci, Barngatan 2 B, SE-22185 Lund, Sweden.
Lund Univ, Sect Oncol & Pathol, Dept Clin Sci, Barngatan 2 B, SE-22185 Lund, Sweden;Lund Univ, CEBMMS, Lund, Sweden.ORCID iD: 0000-0001-9626-0576
Lund Univ, Sect Oncol & Pathol, Dept Clin Sci, Barngatan 2 B, SE-22185 Lund, Sweden.
Lund Univ, Sect Oncol & Pathol, Dept Clin Sci, Barngatan 2 B, SE-22185 Lund, Sweden.
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2019 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 25, no 10, p. 3115-3127Article in journal (Refereed) Published
Abstract [en]

Purpose: 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 noninvasive diagnosis of glioma. Experimental Design: 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-based ultrasensitive immunoprofiling of plEV proteins that was applied on a well-defined glioma study cohort (n = 82). Results: 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; area under the ROC curve (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 plEV(SDC1) originating from GBM tumors, as plEVSDC1 correlated with SDC1 protein expression in matched patient tumors, and plEV(SDC1) was decreased postoperatively depending on the extent of surgery. Conclusions: Our studies support the concept of circulating plEVs as a tool for noninvasive diagnosis and monitoring of gliomas and should move this field closer to the goal of improving the management of cancer patients.

Place, publisher, year, edition, pages
2019. Vol. 25, no 10, p. 3115-3127
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Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-387278DOI: 10.1158/1078-0432.CCR-18-2946ISI: 000468064200021PubMedID: 30679164OAI: oai:DiVA.org:uu-387278DiVA, id: diva2:1329444
Funder
Swedish Research Council, VR-MH 2014-3421Swedish Research Council, K2011-52X-21737-01-3EU, Horizon 2020Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24Bibliographically approved

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Freyhult, EvaBelting, Mattias

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