title: Plasma exosomal miR-21 and miR-181a differentiates follicular from papillary thyroid cancer.
abstract: 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.
authors.affiliation: Oncosystem Ltd, Hoshimina 11/1-207, Saint-Petersburg, 194356, Russia.|NN Petrov Institute of Oncology, Leningradskaya 68, Saint-Petersburg, 197758, Russia.
authors.forename: Roman
authors.initials: R
authors.lastname: Samsonov
authors.affiliation: FSBI Petersburg Nuclear Physics Institute, Gatchina, Saint-Petersburg, 188300, Russia.|Peter the Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, Saint-Petersburg, 195251, Russia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Burdakov
authors.affiliation: FSBI Petersburg Nuclear Physics Institute, Gatchina, Saint-Petersburg, 188300, Russia.|Peter the Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, Saint-Petersburg, 195251, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Shtam
authors.affiliation: NN Petrov Institute of Oncology, Leningradskaya 68, Saint-Petersburg, 197758, Russia.
authors.forename: Zamira
authors.initials: Z
authors.lastname: Radzhabovа
authors.affiliation: NN Petrov Institute of Oncology, Leningradskaya 68, Saint-Petersburg, 197758, Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Vasilyev
authors.affiliation: NN Petrov Institute of Oncology, Leningradskaya 68, Saint-Petersburg, 197758, Russia.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Tsyrlina
authors.affiliation: Institute of Molecular and Cellular Biology SB RAS, Lavrentieva 8/2, Novosibirsk, 630090, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Titov
authors.affiliation: Institute of Molecular and Cellular Biology SB RAS, Lavrentieva 8/2, Novosibirsk, 630090, Russia.
authors.forename: Michail
authors.initials: M
authors.lastname: Ivanov
authors.affiliation: NN Petrov Institute of Oncology, Leningradskaya 68, Saint-Petersburg, 197758, Russia.
authors.forename: Lev
authors.initials: L
authors.lastname: Berstein
authors.affiliation: FSBI Petersburg Nuclear Physics Institute, Gatchina, Saint-Petersburg, 188300, Russia.|Peter the Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, Saint-Petersburg, 195251, Russia.
authors.forename: Michael
authors.initials: M
authors.lastname: Filatov
authors.affiliation: Institute of Molecular and Cellular Biology SB RAS, Lavrentieva 8/2, Novosibirsk, 630090, Russia.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Kolesnikov
authors.affiliation: Faculty of Medicine in the Galilee, Bar-Ilan University, Henrietta Szold 8, Safed, 13100, Israel.
authors.forename: Hava
authors.initials: H
authors.lastname: Gil-Henn
authors.affiliation: Oncosystem Ltd, Hoshimina 11/1-207, Saint-Petersburg, 194356, Russia. anastasia@malek.com.|NN Petrov Institute of Oncology, Leningradskaya 68, Saint-Petersburg, 197758, Russia. anastasia@malek.com.|Faculty of Medicine in the Galilee, Bar-Ilan University, Henrietta Szold 8, Safed, 13100, Israel. anastasia@malek.com.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Malek
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics*; D000328:Adult; D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary; D003937:Diagnosis, Differential; D055354:Exosomes / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C524940:MIRN21 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs
keywords: Diagnostics; Exosomes; MicroRNA; Thyroid cancer