Plasma exosomal miR-21 and miR-181a differentiates follicular from papillary thyroid cancer
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Thyroid cancer (TC) is the most common endocrine malignancy and its incidence has increased over the last few decades. As has been revealed by a number of studies, TC tissue’s micro-RNA (miRNA) profile may reflect histological features and the clinical behavior of tumor. However, alteration of the miRNA profile of plasma exosomes associated with TC development has to date not been explored. We isolated exosomes from plasma and assayed their characteristics using laser diffraction particle size analysis, atomic force microscopy, and western blotting. Next, we profiled cancer-associated miRNAs in plasma exosomes obtained from papillary TC patients, before and after surgical removal of the tumor. The diagnostic value of selected miRNAs was evaluated in a large cohort of patients displaying different statuses of thyroid nodule disease. MiRNA assessment was performed by RT-qPCR. In total, 60 patients with different types of thyroid nodal pathology were included in the study. Our results revealed that the development of papillary TC is associated with specific changes in exosomal miRNA profiles; this phenomenon can be used for differential diagnostics. MiRNA-31 was found to be over-represented in the plasma exosomes of patients with papillary TC vs. benign tumors, while miRNA-21 helped to distinguish between benign tumors and follicular TC. MiRNA-21 and MiRNA-181a-5p were found to be expressed reciprocally in the exosomes of patients with papillary and follicular TC, and their comparative assessment may help to distinguish between these types of TC with 100 % sensitivity and 77 % specificity.
KeywordsThyroid cancer Exosomes MicroRNA Diagnostics
This study was supported by Oncosystem Ltd. for (to R.S. and A.M.) and by grants from the Helmsley Trust Fund (to H.G.H).
Compliance with ethical standards
The study had Ethical Committee of N.N. Petrov Institute of Oncology approval. Informed consent was obtained from all individual participants included in the study.
Conflicts of interest
- 15.Cantara S, Pilli T, Sebastiani G, Cevenini G, Busonero G, Cardinale S, et al. Circulating miRNA95 and miRNA190 are sensitive markers for the differential diagnosis of thyroid nodules in a Caucasian population. J Clin Endocrinol Metab. 2014;99(11):4190–8. doi: 10.1210/jc.2014-1923.CrossRefPubMedGoogle Scholar
- 25.Whiteside TL. The potential of tumor-derived exosomes for noninvasive cancer monitoring. Expert Rev Mol Diagn. 2015;1293:310.Google Scholar
- 35.Kosaka N. Decoding the secret of cancer by means of extracellular vesicles. J Clin Med. 2016;5(2). doi: 10.3390/jcm5020022.
- 38.Agretti P, Ferrarini E, Rago T, Candelieri A, De Marco G, Dimida A, et al. MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration. Eur J Endocrinol. 2012;167(3):393–400. doi: 10.1530/EJE-12-0400.CrossRefPubMedGoogle Scholar
- 41.Taverna S, Giallombardo M, Gil-Bazo I, Carreca AP, Castiglia M, Chacartegui J, et al. Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: critical analysis of evidence and potential role in clinical practice. Oncotarget. 2016. 10.18632/oncotarget.7638.Google Scholar
- 44.Lozupone F, Kont V, Logozzi A, Talpsepp K, Oja T, Kubo A, et al. TM9SF4 level of expression on exosomes as new marker of malignancy in human cancer. First scientific meeting of ISEV-International Society for Extracellular Vesicles April 18-21 2012. Gothenburg: University of Gothenburg; 2012. p. 19.Google Scholar