Review Article

Extracellular Vesicles and Their Potential Use in Monitoring Cancer Progression and Therapy: The Contribution of Proteomics

Table 3

Summary of the most significant study designs used to analyze the EV proteome, including potential biomarkers identified.

ReferenceBiofluidPathological conditionIsolation techniqueEV subtypeMS-based strategyCandidate biomarkers

Sun et al. [43]Saliva and serumLung CancerPureEXO® isolation kit (101Bio)ExoESI-QTOF MS (MaXis Impact)
LC-MS/MS (Q Exactive)
Vimentin, Phospholipid transfer protein, Annexin, Zinc-alpha-2-glycoprotein, Lactoperoxidase, Proteasome subunit alpha, Grancalcin, Cysteine-rich secretory protein 3, Calpain small subunit 1, Histone H3
Sun et al. [13]SalivaLung CancerUltracentrifugationExo and MVsLC-MS/MS (Q Exactive)Ras GTPase-activating-like protein, BPI fold-containing family A member 1, Cornulin, Mucin-5B
Raimondo et al. [44]UrineRenal Cell CarcinomaIodixanol density centrifugationExoLC-ESI-MS/MS (MaXis hybrid UHR-QTOF)Matrix metalloproteinase-9, Ceruloplasmin, Podocalyxin, Dickkopf related protein 4, Carbonic Anhydrase IX, Aquaporin-1, Extracellular Matrix Metalloproteinase Inducer, Neprilysin, Dipeptidase 1, Syntenin-1
Chen et al. [45]SerumColorectal CancerUltracentrifugationExoHPLC-MS/MS (Orbitrap Fusion)Fibronectin-1, Annexin-A1, Metalloproteinase-9, Galectin-3
binding protein, Insulin-like growth factor
Aqrawi et al. [11]Saliva and tearSjögren’s SyndromeSize-exclusion chromatographyExo and MVsLC-MS/MS (Q Exactive)Lymphocyte-specific protein 1, Adipocyte plasma membrane-associated protein, Copine-1, Thioredoxin-dependent peroxidase reductase
Choi et al. [46]AscitesColorectal CancerIodixanol and sucrose density centrifugationMVsLC-ESI-MS/MS (LTQ)Carcinoembryonic antigen cell adhesion molecule 5, Adhesion G-protein-coupled receptor E5, Galectin-3, Epithelial cell adhesion molecule, Aminopeptidase N, Trophoblast glycoprotein
Kittivorapart et al. [47]PlasmaHbE/β- thalassaemiaUltracentrifugationNon specifiedHPLC-MS/MS (Orbitrap Fusion)Alpha hemoglobin–stabilizing protein, Catalase, Superoxide dismutase, Hemopexin, Haptoglobin
Shiromizu et al. [48]SerumColorectal CancerSucrose density centrifugationNot specifiedLC-MS/MS (Q Exactive)Annexin-A3, A4, A5 and A11, Tenascin-N, Mucin-5B, Matrix metalloproteinase-9, Transferrin receptor protein 1
Sequeiros et al. [49]UrineProstate CancerUltracentrifugationNot specifiedSRM-MS (5500 Q-Trap)Adseverin, Transglutaminase-4
Arbelaiz et al. [50]SerumCholangiocarcinoma (CCA)
Primary Sclerosing Cholangitis (PSC)
Hepatocellular carcinoma (HCC)
UltracentrifugationNot specifiedUPLC-MS/MS (LTQ Orbitrap XL and Synapt G2-Si)CCA: Aminopeptidase N, Pantetheinase, Polymeric immunoglobulin receptor
PSC: Ficolin-1, Neprilysin, Fibrinogen gamma chain, Alpha-1-acid glycoprotein 1, S100A8 proteins
HCC: Galectin-3-binding protein, Polymeric immunoglobulin receptor
Yang et al. [51]Seminal fluidProstate CancerSucrose density centrifugationExoHPLC-MS/MS (LTQ Orbitrap Elite)Semenogelin-1, Phosphoglycerate dehydrogenase, Galectin-3-binding protein, Actin, Glyceraldehyde-3-phosphate dehydrogenase
Barnabas et al. [52]Uterine Liquid BiopsyOvarian CancerUltracentrifugationMVsLC-MS/MS (Q Exactive)Calcium-activated chloride channel regulator 4, Involucrin, Protein S100-A14, Protein S100-A2, Serpin B5
Turay et al. [53]PlasmaProstate CancerExoquick™ Isolation KitExoHPLC-MS/MS (LCQ Deca XP)Iroquois homeobox protein 5, Mitochondrial tumor suppressor 1 isoform 4, Trinucleotide repeat containing 6B isoform 3

ESI, electrospray ionization; QTOF, quadrupole time-of-flight; LTQ, linear trap quadrupole; SRM, selected reaction monitoring.