**5. Extracellular vesicles in biomarkers in cancer diagnosis**

EVs have gained extensive attention as promising biomarkers for cancer diagnostics. Characteristics of EV include their relatively short-lived or highly labile in the cytoplasm of donor cells make them a stable biomarker cargo, be it protein, lipid, nucleic acid. In cancer these molecules can be reflective of both the tumors presence and also of cancer staging. Some studies have demonstrated that biomolecules in serum or plasma exosomes are of great value for tumor diagnosis including long non-coding RNAs (lncRNAs), miRNAs, and proteins [96]. Some other important properties of EVs which make researchers believe they represent cancer biomarkers are: (a) most of EVs populations are shed from all cell types in the organism; (b) molecular determinants contained in EVs are dependent on cells/tissues of origin; (c) however the specific EVs cargo (i.e. proteins, miRNAs) is not always coupled to the overexpression in the cells of origin; (d) molecular cargos in EVs can be affected by microenvironment conditions such as inflammation, oxygen deprivation, and metabolic balance; (e) EVs size may affect their content. In several cancers, including ovarian cancer, it has been demonstrated that the expression of a specific subset of miRNAs may potentially be used in clinical practice, for example, for screening or early diagnosis to evaluate the response to therapeutic treatments. EVs in blood and urine of prostate cancer patients contain unique prostate-cancer specific contents that are biomarkers of prostate cancer [97, 98]. EVs are proving to be valuable diagnostic biomarker in pancreatic cancer; flow cytometry coupled with mass spectrometry analysis of exosome glypican-1 can distinguish benign disease from early and late stage cancer [99]. Again, the detection of DEL-1 on circulating EVs facilitated early-stage breast cancer diagnosis and discrimination of breast cancer from benign breast disease [100]. EV-survivin is proposed to be useful in breast cancer diagnosis [101]. Kibria et al. also suggested that EV-CD47 may be a possible breast cancer biomarker [102].
