{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:05:02Z","timestamp":1789733102982,"version":"4.0.1"},"reference-count":41,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["20-14-00074-P"],"award-info":[{"award-number":["20-14-00074-P"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 &lt; 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 &lt; p &lt; 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.<\/jats:p>","DOI":"10.3390\/ijms25137090","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T03:42:30Z","timestamp":1719546150000},"page":"7090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Prediction of the Aggressive Clinical Course of Papillary Thyroid Carcinoma Based on Fine Needle Aspiration Biopsy Molecular Testing"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5559-9872","authenticated-orcid":false,"given":"Sergei A.","family":"Lukyanov","sequence":"first","affiliation":[{"name":"Department of General and Pediatric Surgery, South Ural State Medical University, Chelyabinsk 454092, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-5737","authenticated-orcid":false,"given":"Sergei E.","family":"Titov","sequence":"additional","affiliation":[{"name":"Department of the Structure and Function of Chromosomes, Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk 630090, Russia"},{"name":"PCR Laboratory, AO Vector-Best, Novosibirsk 630117, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3659-7510","authenticated-orcid":false,"given":"Evgeniya S.","family":"Kozorezova","sequence":"additional","affiliation":[{"name":"National Center of Clinical Morphological Diagnostics, Saint Petersburg 192283, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9433-8341","authenticated-orcid":false,"given":"Pavel S.","family":"Demenkov","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia"},{"name":"Institute of Cytology and Genetics, SB RAS, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3799-9407","authenticated-orcid":false,"given":"Yulia A.","family":"Veryaskina","sequence":"additional","affiliation":[{"name":"Department of the Structure and Function of Chromosomes, Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk 630090, Russia"},{"name":"Institute of Cytology and Genetics, SB RAS, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2198-4793","authenticated-orcid":false,"given":"Denis V.","family":"Korotovskii","sequence":"additional","affiliation":[{"name":"Department of General and Pediatric Surgery, South Ural State Medical University, Chelyabinsk 454092, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana E.","family":"Ilyina","sequence":"additional","affiliation":[{"name":"Department of General and Pediatric Surgery, South Ural State Medical University, Chelyabinsk 454092, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey L.","family":"Vorobyev","sequence":"additional","affiliation":[{"name":"National Center of Clinical Morphological Diagnostics, Saint Petersburg 192283, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir A.","family":"Zhivotov","sequence":"additional","affiliation":[{"name":"Department of Surgery, National Medical and Surgical Center Named after N.I. Pirogov, Moscow 105203, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita S.","family":"Bondarev","sequence":"additional","affiliation":[{"name":"Department of Surgery, National Medical and Surgical Center Named after N.I. Pirogov, Moscow 105203, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya V.","family":"Sleptsov","sequence":"additional","affiliation":[{"name":"Department of Faculty Surgery, Saint Petersburg State University, Saint Petersburg 199034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei V.","family":"Sergiyko","sequence":"additional","affiliation":[{"name":"Department of General and Pediatric Surgery, South Ural State Medical University, Chelyabinsk 454092, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/thy.2015.0020","article-title":"2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer","volume":"26","author":"Haugen","year":"2016","journal-title":"Thyroid"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1001\/archoto.2010.55","article-title":"Thyroid cancer survival in the United States: Observational data from 1973 to 2005","volume":"136","author":"Davies","year":"2010","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"925","DOI":"10.6004\/jnccn.2022.0040","article-title":"Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology","volume":"20","author":"Haddad","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.bj.2021.11.009","article-title":"Evaluation of recurrence risk in patients with papillary thyroid cancer through tumor-node-metastasis staging: A single-center observational study in Taiwan","volume":"45","author":"Sun","year":"2022","journal-title":"Biomed. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1001\/jamasurg.2018.1153","article-title":"Performance of a genomic sequencing classifier for the preoperative diagnosis of cytologically indeterminate thyroid nodules","volume":"153","author":"Patel","year":"2018","journal-title":"JAMA Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1530\/EJE-15-1163","article-title":"Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests","volume":"174","author":"Valderrabano","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1097\/SLA.0000000000003580","article-title":"The American Association of Endocrine Surgeons Guidelines for the definitive surgical management of thyroid disease in adults","volume":"271","author":"Patel","year":"2020","journal-title":"Ann. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5831","DOI":"10.1002\/cam4.2467","article-title":"Spectrum of TERT promoter mutations and mechanisms of activation in thyroid cancer","volume":"8","author":"Panebianco","year":"2019","journal-title":"Cancer Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E754","DOI":"10.1210\/jc.2013-3734","article-title":"TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas","volume":"99","author":"Melo","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.surg.2016.04.054","article-title":"Preoperative detection of RAS mutation may guide extent of thyroidectomy","volume":"161","author":"Patel","year":"2017","journal-title":"Surgery"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1002\/cncr.29934","article-title":"Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients","volume":"122","author":"Song","year":"2016","journal-title":"Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/SLA.0000000000001420","article-title":"Tumor genotype determines phenotype and disease-related outcomes in thyroid cancer: A study of 1510 patients","volume":"262","author":"Yip","year":"2015","journal-title":"Ann. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1001\/jamaoto.2023.1494","article-title":"Prognostic Value of Preoperative Molecular Testing and Implications for Initial Surgical Management in Thyroid Nodules Harboring Suspected (Bethesda V) or Known (Bethesda VI) Papillary Thyroid Cancer","volume":"149","author":"Schumm","year":"2023","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1002\/cncr.33421","article-title":"Risk assessment for distant metastasis in differentiated thyroid cancer using molecular profiling: A matched case-control study","volume":"127","author":"Yip","year":"2021","journal-title":"Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1089\/thy.2023.0060","article-title":"Molecular Testing Predicts Incomplete Response to Initial Therapy in Differentiated Thyroid Carcinoma Without Lateral Neck or Distant Metastasis at Presentation: Retrospective Cohort Study","volume":"33","author":"Liu","year":"2023","journal-title":"Thyroid"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R415","DOI":"10.1530\/ERC-19-0093","article-title":"DNA methylation in thyroid cancer","volume":"26","author":"Zafon","year":"2019","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rogucki, M., Buczy\u0144ska, A., Kr\u0119towski, A.J., and Pop\u0142awska-Kita, A. (2021). The Importance of miRNA in the Diagnosis and Prognosis of Papillary Thyroid Cancer. J. Clin. Med., 10.","DOI":"10.3390\/jcm10204738"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1210\/clinem\/dgab836","article-title":"Recurrence of Papillary Thyroid Cancer: A Systematic Appraisal of Risk Factors","volume":"107","author":"Nieto","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Titov, S.E., Ivanov, M.K., Demenkov, P.S., Katanyan, G.A., Kozorezova, E.S., Malek, A.V., Veryaskina, Y.A., and Zhimulev, I.F. (2019). Combined quantitation of HMGA2 mRNA, microRNAs, and mitochondrial-DNA content enables the identification and typing of thyroid tumors in fine-needle aspiration smears. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6154-7"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ravi, N., Yang, M., Mylona, N., Wennerberg, J., and Paulsson, K. (2020). Global RNA Expression and DNA Methylation Patterns in Primary Anaplastic Thyroid Cancer. Cancers, 12.","DOI":"10.3390\/cancers12030680"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wojtas, B., Pfeifer, A., Oczko-Wojciechowska, M., Krajewska, J., Czarniecka, A., Kukulska, A., Eszlinger, M., Musholt, T., Stokowy, T., and Swierniak, M. (2017). Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061184"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1530\/EC-17-0261","article-title":"A six-gene panel to label follicular adenoma, low- and high-risk follicular thyroid carcinoma","volume":"7","author":"Poma","year":"2018","journal-title":"Endocr. Connect."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1111\/cas.14501","article-title":"Causative role for defective expression of mitochondria-eating protein in accumulation of mitochondria in thyroid oncocytic cell tumors","volume":"111","author":"Mussazhanova","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nan, B.Y., Xiong, G.F., Zhao, Z.R., Gu, X., and Huang, X.S. (2021). Comprehensive Identification of Potential Crucial Genes and miRNA-mRNA Regulatory Networks in Papillary Thyroid Cancer. Biomed Res. Int., 2021.","DOI":"10.1155\/2021\/6752141"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ma, J., Han, W., and Lu, K. (2021). Comprehensive Pan-Cancer Analysis and the Regulatory Mechanism of ASF1B, a Gene Associated With Thyroid Cancer Prognosis in the Tumor Micro-Environment. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.711756"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1089\/thy.2019.0490","article-title":"A Thyroid Genetic Classifier Correctly Predicts Benign Nodules with Indeterminate Cytology: Two Independent, Multicenter, Prospective Validation Trials","volume":"30","author":"Zafereo","year":"2020","journal-title":"Thyroid"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/01.sla.0000179623.87329.6b","article-title":"ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy","volume":"242","author":"Kebebew","year":"2005","journal-title":"Ann. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1159\/000093056","article-title":"Molecular markers for discrimination of benign and malignant follicular thyroid tumors","volume":"27","author":"Gustafsson","year":"2006","journal-title":"Tumour Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s13046-020-01757-x","article-title":"The molecular and gene\/miRNA expression profiles of radioiodine resistant papillary thyroid cancer","volume":"39","author":"Colombo","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.gene.2019.04.088","article-title":"Prognostic value of high mobility group protein A2 (HMGA2) over-expression in cancer progression","volume":"706","author":"Binabaj","year":"2019","journal-title":"Gene"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1530\/EC-17-0302","article-title":"NIS expression in thyroid tumors, relation with prognosis clinicopathological and molecular features","volume":"7","author":"Tavares","year":"2018","journal-title":"Endocr. Connect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.21037\/tcr.2018.09.12","article-title":"The construction and analysis of gene co-expression network of differentially expressed genes identifies potential biomarkers in thyroid cancer","volume":"7","author":"Chai","year":"2018","journal-title":"Transl. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1158\/1078-0432.CCR-18-0373","article-title":"Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers","volume":"24","author":"Pozdeyev","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s12020-018-1644-y","article-title":"Survival of aggressive variants of papillary thyroid carcinoma in patients under 55 years old: A SEER population-based retrospective analysis","volume":"61","author":"Feng","year":"2018","journal-title":"Endocrine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12022-022-09707-3","article-title":"Overview of the 2022 WHO Classification of Thyroid Neoplasms","volume":"33","author":"Baloch","year":"2022","journal-title":"Endocr. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1089\/thy.2019.0459","article-title":"Risk Stratifcation Using a Novel Genetic Classifer Including PLEKHS1 Promoter Mutations for Diferentiated Thyroid Cancer with Distant Metastasis","volume":"30","author":"Jung","year":"2020","journal-title":"Thyroid"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2052396","DOI":"10.1155\/2020\/2052396","article-title":"Differential MicroRNA-Signatures in Thyroid Cancer Subtypes","volume":"2020","author":"Santiago","year":"2020","journal-title":"J. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"93","DOI":"10.17650\/2222-1468-2020-10-1-93-100","article-title":"Stratification of papillary thyroid cancer relapse risk based on the results of molecular genetic studies","volume":"10","author":"Lukyanov","year":"2020","journal-title":"Head Neck Tumors"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1136\/jclinpath-2020-206445","article-title":"Preoperative detection of malignancy in fine-needle aspiration cytology (FNAC) smears with indeterminate cytology (Bethesda III, IV) by a combined molecular classifier","volume":"73","author":"Titov","year":"2020","journal-title":"J. Clin. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e179","DOI":"10.1093\/nar\/gni178","article-title":"Real-time quantification of microRNAs by stem-loop RT-PCR","volume":"33","author":"Chen","year":"2005","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7090\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:06:45Z","timestamp":1760108805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,28]]},"references-count":41,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25137090"],"URL":"https:\/\/doi.org\/10.3390\/ijms25137090","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,28]]}}}