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Open AccessArticle

Small Extracellular Vesicles Isolated from Serum May Serve as Signal-Enhancers for the Monitoring of CNS Tumors

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Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre, H-6726 Szeged, Hungary
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Department of Medical Genetics, Doctoral School of Interdisciplinary Medicine, University of Szeged, H-6720 Szeged, Hungary
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Department of Medical Chemistry, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary
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Department of Neurosurgery, Clinical Centre, University of Debrecen, H-4032 Debrecen, Hungary
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Department of Medical Physics and Informatics, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary
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Department of Medical Physics and Informatics, Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Hungary
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Department of Immunology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
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Department of Immunology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary
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Department of Immunology, Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Hungary
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(15), 5359; https://doi.org/10.3390/ijms21155359
Received: 26 June 2020 / Revised: 17 July 2020 / Accepted: 24 July 2020 / Published: 28 July 2020
(This article belongs to the Special Issue Extracellular Vesicles: Biology and Potentials in Cancer Therapeutics)
Liquid biopsy-based methods to test biomarkers (e.g., serum proteins and extracellular vesicles) may help to monitor brain tumors. In this proteomics-based study, we aimed to identify a characteristic protein fingerprint associated with central nervous system (CNS) tumors. Overall, 96 human serum samples were obtained from four patient groups, namely glioblastoma multiforme (GBM), non-small-cell lung cancer brain metastasis (BM), meningioma (M) and lumbar disc hernia patients (CTRL). After the isolation and characterization of small extracellular vesicles (sEVs) by nanoparticle tracking analysis (NTA) and atomic force microscopy (AFM), liquid chromatography -mass spectrometry (LC-MS) was performed on two different sample types (whole serum and serum sEVs). Statistical analyses (ratio, Cohen’s d, receiver operating characteristic; ROC) were carried out to compare patient groups. To recognize differences between the two sample types, pairwise comparisons (Welch’s test) and ingenuity pathway analysis (IPA) were performed. According to our knowledge, this is the first study that compares the proteome of whole serum and serum-derived sEVs. From the 311 proteins identified, 10 whole serum proteins and 17 sEV proteins showed the highest intergroup differences. Sixty-five proteins were significantly enriched in sEV samples, while 129 proteins were significantly depleted compared to whole serum. Based on principal component analysis (PCA) analyses, sEVs are more suitable to discriminate between the patient groups. Our results support that sEVs have greater potential to monitor CNS tumors, than whole serum. View Full-Text
Keywords: extracellular vesicles; cancer biomarker; proteomics extracellular vesicles; cancer biomarker; proteomics
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Dobra, G.; Bukva, M.; Szabo, Z.; Bruszel, B.; Harmati, M.; Gyukity-Sebestyen, E.; Jenei, A.; Szucs, M.; Horvath, P.; Biro, T.; Klekner, A.; Buzas, K. Small Extracellular Vesicles Isolated from Serum May Serve as Signal-Enhancers for the Monitoring of CNS Tumors. Int. J. Mol. Sci. 2020, 21, 5359.

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