Prediction of the Aggressive Clinical Course of Papillary Thyroid Carcinoma Based on Fine Needle Aspiration Biopsy Molecular Testing

Author:

Lukyanov Sergei A.1ORCID,Titov Sergei E.234ORCID,Kozorezova Evgeniya S.5ORCID,Demenkov Pavel S.46ORCID,Veryaskina Yulia A.26ORCID,Korotovskii Denis V.1ORCID,Ilyina Tatyana E.1,Vorobyev Sergey L.5,Zhivotov Vladimir A.7,Bondarev Nikita S.7,Sleptsov Ilya V.8,Sergiyko Sergei V.1

Affiliation:

1. Department of General and Pediatric Surgery, South Ural State Medical University, Chelyabinsk 454092, Russia

2. Department of the Structure and Function of Chromosomes, Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk 630090, Russia

3. PCR Laboratory, AO Vector-Best, Novosibirsk 630117, Russia

4. Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia

5. National Center of Clinical Morphological Diagnostics, Saint Petersburg 192283, Russia

6. Institute of Cytology and Genetics, SB RAS, Novosibirsk 630090, Russia

7. Department of Surgery, National Medical and Surgical Center Named after N.I. Pirogov, Moscow 105203, Russia

8. Department of Faculty Surgery, Saint Petersburg State University, Saint Petersburg 199034, Russia

Abstract

Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcomes, which opens up new avenues for using them in the personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in the preoperative diagnosis of aggressive variants of papillary thyroid cancer. The molecular genetic profile (expression levels of 34 different markers and BRAF mutations) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Statistically significant differences with adjustment for multiple comparisons (p < 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, fibronectin 1 (FN1), and cyclin-dependent kinase inhibitor 2A (CDKN2A) genes. A weak statistical correlation (0.0015 < p < 0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, FN1, and CDKN2A genes.

Funder

Russian Science Foundation

Publisher

MDPI AG

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