**10. Expression of microRNAs in serum**

One of the goals within cancer study is to develop non-invasive tests for the diagnosis and follow-up of patients; because of this, there is a great interest in the detection of nucleic acids that are circulating in serum and plasma. Serum and plasma contain a great number of stable miRNAs, despite the high content of ribonucleases in the plasma. This stability may be given by finding itself within the exosomes (organelles derived from endosomes), by chemical modifications or by associating with protein complexes such as RISC [60, 61]. Lawrie et al. [4] reported their first study regarding miRNAs, associated with tumours, in lymphoma patients' serums, and they found that the levels of miR-155, miR-210 and miR-21 were higher than those found in control serums of healthy patients. In this study, they related the high expression of miR-21 with a better prognosis. These results were consistent with previous results in biopsy material from lymphoma patients, in which high levels of miR-21 were associated with a better prognosis [4]. Chen et al. detected and sequenced 100 miRNAs in healthy patients' serums and in patients with lung and colorectal cancers, reporting specific expression patterns of tumour type. In this same study, they distinguished the miRNAs in the serums of other species of small nucleotides such as tRNA or downgraded RNA fragments, concluding that miRNAs are the main fraction present in serum [62, 63]. One of the first undertaken studies in astrocytoma patient serums was the one by Skog et al. in which they report that tumour cells on glioblastomas release microvesicles that contain microRNA, RNAm and angiogenic proteins [64]. These results indicate that patients with cancer present elevated levels of exosomes in plasma, derived from the tumour, in comparison with controls. Although normal cells may contribute to the population of exosomes in the peripheral circulation, the main source of circulating exosomes in cancer patients is originated in the tumour. Nevertheless, little is known about the mechanism by which miRNAs are generated in plasma and the biological impact of these molecules in distant sites of the body [61]. The discovery of miRNAs in serum opens the possibility of using them as biomarkers in different illnesses.
