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Patients with HCV-related cirrhosis are at risk for liver cancer development. For these patients miRNAs may serve as preclinical markers, which expression levels are deregulated in cancer and which are stable to the damaging factors partly through complex formation with proteins or packaging into exosomes. In this research we have tried to identify what miRNA fraction in plasma -exosomal or not packed into exosomes (non-exosomal) -is stronger associated with primary liver cancer. The second question was whether saliva miRNA expression levels -both exosomal and non-exosomal -are associated with primary liver cancer. We evaluated exosomal and non-exosomal miRNAs -let-7a-5p, -16-5p, -18a-5p, -21-5p, -22-3p, -34a-5p, -103a-3p, -122-5p, -221-3p, -222-3p -in plasma and saliva of patients with HCVrelated liver cirrhosis (n = 24), primary liver cancer (n = 24) and healthy volunteers (n = 21). Relative expression level was calculated with normalization of exosomal miRNA to exosomal miRNA-16-5p, non-exosomal miRNA to non-exosomal miRNA-16-5p and as a ratio of exosomal miRNA to non-exosomal miRNA. In this study, non-exosomal miRNAs (let-7a, miRNA-21-5p, -22-3p, -103a, -122-5p, -221-3p and 222-3p) normalized to non-exosomal miRNA-16-5p showed strong association with liver cancer in plasma. Three miRNAs, those with the mostly pronounced change of expression levels in plasma, -miRNA-21-5p, 122-5p, 221-3p -were detected in saliva. In contrast, exosomal miRNAs show stronger association with primary liver over non-exosomal miRNAs when working with saliva. Thus, depending on the examined biological material both miRNA fractions may serve as a valuable source for diagnostic and prognostic data.

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This chapter reviewed the various sources of exosomes and their characteristics. Exosomes, which in the context of the proposed chapter are the synonym for extracellular vesicles up to 200 nm, play a pivotal role in cell to cell communication thus leading to the involvement of exosomes in inflammation and cancer development. This brings exosomes to the forefront of promising markers of a sub-clinical stage of the disease, which makes identifying exosome’s source and destination one of the main goals in exosome research. However, due to some biogenesis features and technological difficulties, which are discussed further, identification of a certain exosome’s address, or its specificity for a certain tissue or cell type, becomes a non-trivial task. The chapter covers the following questions: some of the main barriers on the way of testing tissue specificity hypothesis of exosomes, exosomes from synovial fluid and CSF and their features, exosomes from mesenchymal stem cells (MSCs) of different origins, and some membrane and cargo exosomal markers for tissue specificity and the prospect of exosomes as a drug delivery approach.