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

• Published in: International journal of molecular sciences Vol. 21; no. 15; p. 5359
• Main Authors: Dobra, Gabriella, Bukva, Matyas, Szabo, Zoltan, Bruszel, Bella, Harmati, Maria, Gyukity-Sebestyen, Edina, Jenei, Adrienn, Szucs, Monika, Horvath, Peter, Biro, Tamas, Klekner, Almos, Buzas, Krisztina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.07.2020; MDPI
• Subjects: Adult; Aged; Aged, 80 and over; Atomic force microscopy; Atomic properties; Biomarkers; Biomarkers, Tumor - blood; Biopsy; Blood; Brain cancer; Brain research; Brain tumors; cancer biomarker; Cancer therapies; Carcinoma, Non-Small-Cell Lung - blood; Central nervous system; Disease; Extracellular vesicles; Extracellular Vesicles - metabolism; Female; Glioblastoma; Hernia; Humans; Intervertebral discs; Liquid chromatography; Lung cancer; Lung Neoplasms - blood; Male; Mass spectrometry; Mass spectroscopy; Meningeal Neoplasms - blood; Meningeal Neoplasms - secondary; Meningioma; Metastases; Metastasis; Middle Aged; Nanoparticles; Neoplasm Proteins - blood; Ovaries; Pancreatic cancer; Patients; Principal components analysis; Proteins; Proteomes; Proteomics; Serum proteins; Signal monitoring; Statistical analysis; Statistical methods; Tumors; Vesicles; proteomics; cancer biomarker; extracellular vesicles
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21155359

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.