{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:18:58Z","timestamp":1790360338957,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004252","name":"Qatar University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004252","id-type":"DOI","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/00yhnba62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Thyroid cancer comprises a biologically diverse group of tumors initiated by a limited number of recurrent driver alterations, with additional molecular events promoting dedifferentiation, therapeutic resistance, and aggressive clinical behavior. Advances in tumor sequencing have clarified the molecular architecture of papillary, follicular, oncocytic, poorly differentiated, anaplastic, and medullary thyroid carcinomas, and have already changed management in selected settings. Molecular testing improves diagnostic refinement and risk assessment in cytologically indeterminate thyroid nodules, while alterations involving BRAF, RET, and NTRK can guide targeted therapy in advanced disease. Beyond DNA, transcriptomic, proteomic, epigenetic, metabolomic, immune, spatial, and liquid-biopsy approaches offer functional insight into differentiation state, treatment sensitivity, and resistance, although most remain investigational. Their clinical value depends not only on biological plausibility, but on reproducibility, incremental value beyond established clinicopathological variables, and the ability to alter patient management. Computational tools may further support integration of molecular and clinical data, but their usefulness likewise depends on calibration, external validation, interpretability, and demonstration of decision impact. This review synthesizes the genomic and multi-omics determinants of thyroid cancer management across diagnosis, risk stratification, treatment selection, resistance monitoring, and follow-up, and discusses the practical barriers that continue to limit routine implementation, including assay standardization, cost, access, and real-world feasibility. Progress in precision thyroid oncology will depend on robust validation of emerging biomarkers and clear evidence that they improve patient outcomes.<\/jats:p>","DOI":"10.3390\/ijms27167464","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"7464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genomics and Multi-Omics to Guide Clinical Management in Thyroid Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-9942","authenticated-orcid":false,"given":"Dhoha","family":"Dhieb","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Department, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2646-1123","authenticated-orcid":false,"given":"Kholoud","family":"Bastaki","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Department, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/nrendo.2016.110","article-title":"The changing incidence of thyroid cancer","volume":"12","author":"Kitahara","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/CCO.0000000000000148","article-title":"The changing epidemiology of thyroid cancer","volume":"27","author":"Vigneri","year":"2015","journal-title":"Curr. Opin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1001\/jama.2017.2719","article-title":"Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974-2013","volume":"317","author":"Lim","year":"2017","journal-title":"J. Am. Med. Assoc."},{"key":"ref_5","first-page":"5888","article-title":"The incidence and survival analysis for anaplastic thyroid cancer: A SEER database analysis","volume":"11","author":"Lin","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1093\/annonc\/mdz400","article-title":"Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"30","author":"Filetti","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41574-020-00448-z","article-title":"Current practice in patients with differentiated thyroid cancer","volume":"17","author":"Schlumberger","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1089\/thy.2020.0944","article-title":"2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer","volume":"31","author":"Bible","year":"2021","journal-title":"Thyroid"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1172\/JCI85271","article-title":"Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers","volume":"126","author":"Landa","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_10","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_11","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_12","unstructured":"WHO Classification of Tumours Editorial Board (2022). WHO Classification of Tumours, [5th ed.]."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Juhlin, C.C., Mete, O., and Baloch, Z.W. (2023). The 2022 WHO classification of thyroid tumors: Novel concepts in nomenclature and grading. Endocr.-Relat. Cancer, 30.","DOI":"10.1530\/ERC-22-0293"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1001\/jamaoncol.2018.4616","article-title":"Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology","volume":"5","author":"Steward","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_15","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_16","unstructured":"Cancer Genome Atlas Research Network (2014). Integrated Genomic Characterization of Papillary Thyroid Carcinoma. Cell, 159, 676\u2013690."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6251","DOI":"10.7150\/thno.57689","article-title":"Molecular mechanisms of radioactive iodine refractoriness in differentiated thyroid cancer: Impaired sodium iodide symporter (NIS) expression owing to altered signaling pathway activity and intracellular localization of NIS","volume":"11","author":"Oh","year":"2021","journal-title":"Theranostics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E1562","DOI":"10.1210\/jc.2013-2383","article-title":"Frequent Somatic TERT Promoter Mutations in Thyroid Cancer: Higher Prevalence in Advanced Forms of the Disease","volume":"98","author":"Landa","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1038\/s41467-019-10680-5","article-title":"Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer","volume":"10","author":"Yoo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1158\/2159-8290.CD-20-0735","article-title":"SWI\/SNF Complex Mutations Promote Thyroid Tumor Progression and Insensitivity to Redifferentiation Therapies","volume":"11","author":"Saqcena","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.annonc.2021.12.014","article-title":"Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: Updated analysis from the phase II ROAR basket study","volume":"33","author":"Subbiah","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1530\/EJE-21-1259","article-title":"Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma","volume":"186","author":"Waguespack","year":"2022","journal-title":"Eur. J. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102380","DOI":"10.1016\/j.ctrv.2022.102380","article-title":"Molecular diagnosis and targeted treatment of advanced follicular cell-derived thyroid cancer in the precision medicine era","volume":"106","author":"Capdevila","year":"2022","journal-title":"Cancer Treat. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1056\/NEJMoa2005651","article-title":"Efficacy of Selpercatinib in RET -Altered Thyroid Cancers","volume":"383","author":"Wirth","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1056\/NEJMoa1209288","article-title":"Selumetinib-Enhanced Radioiodine Uptake in Advanced Thyroid Cancer","volume":"368","author":"Ho","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1158\/1078-0432.CCR-23-0046","article-title":"A Phase II Redifferentiation Trial with Dabrafenib-Trametinib and 131I in Metastatic Radioactive Iodine Refractory BRAF p.V600E-Mutated Differentiated Thyroid Cancer","volume":"29","author":"Leboulleux","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1089\/thy.2019.0514","article-title":"Acquired Secondary RAS Mutation in BRAF V600E -Mutated Thyroid Cancer Patients Treated with BRAF Inhibitors","volume":"30","author":"Cabanillas","year":"2020","journal-title":"Thyroid"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1089\/thy.2020.0296","article-title":"Clinical Utility of Circulating Cell-Free DNA Mutations in Anaplastic Thyroid Carcinoma","volume":"31","author":"Qin","year":"2021","journal-title":"Thyroid"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1158\/1541-7786.MCR-21-0442","article-title":"Genomic and Transcriptomic Correlates of Thyroid Carcinoma Evolution after BRAF Inhibitor Therapy","volume":"20","author":"Lee","year":"2021","journal-title":"Mol. Cancer Res."},{"key":"ref_31","first-page":"R173","article-title":"Molecular mechanisms of resistance to kinase inhibitors in thyroid cancers","volume":"29","author":"Hofmann","year":"2022","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Fugazzola, L. (2022). Medullary thyroid cancer - An update. Best Pr. Res. Clin. Endocrinol. Metab., 37.","DOI":"10.1016\/j.beem.2022.101655"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s12022-024-09836-x","article-title":"Consensus Statement: Recommendations on Actionable Biomarker Testing for Thyroid Cancer Management","volume":"35","author":"Mete","year":"2024","journal-title":"Endocr. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12022-023-09753-5","article-title":"Update on C-Cell Neuroendocrine Neoplasm: Prognostic and Predictive Histopathologic and Molecular Features of Medullary Thyroid Carcinoma","volume":"34","author":"Jung","year":"2023","journal-title":"Endocr. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1200\/JCO.21.01861","article-title":"Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers","volume":"40","author":"Franco","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"705\u2013+","DOI":"10.1126\/science.abg2538","article-title":"Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident","volume":"372","author":"Morton","year":"2021","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1200\/JCO.2014.55.5094","article-title":"BRAF V600E and TERT Promoter Mutations Cooperatively Identify the Most Aggressive Papillary Thyroid Cancer with Highest Recurrence","volume":"32","author":"Xing","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1158\/1078-0432.CCR-14-2915","article-title":"Redifferentiation of Iodine-Refractory BRAF V600E-Mutant Metastatic Papillary Thyroid Cancer with Dabrafenib","volume":"21","author":"Rothenberg","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12022-020-09661-y","article-title":"Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates","volume":"32","author":"Mete","year":"2021","journal-title":"Endocr. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1210\/jc.2018-00277","article-title":"Comprehensive Genetic Analysis of Follicular Thyroid Carcinoma Predicts Prognosis Independent of Histology","volume":"103","author":"Nicolson","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1530\/ERC-16-0043","article-title":"Prevalence and phenotypic correlations of EIF1AX mutations in thyroid nodules","volume":"23","author":"Karunamurthy","year":"2016","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41379-021-00907-6","article-title":"Molecular classification of follicular thyroid carcinoma based on TERT promoter mutations","volume":"35","author":"Park","year":"2021","journal-title":"Mod. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ccell.2018.06.013","article-title":"Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in H\u00fcrthle Cell Carcinoma","volume":"34","author":"Gopal","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1158\/2159-8290.CD-22-0982","article-title":"Mitochondrial-Encoded Complex I Impairment Induces a Targetable Dependency on Aerobic Fermentation in H\u00fcrthle Cell Carcinoma of the Thyroid","volume":"13","author":"Frank","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4233","DOI":"10.1073\/pnas.1321937111","article-title":"Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer","volume":"111","author":"Kelly","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1089\/thy.2020.0086","article-title":"Dissecting Anaplastic Thyroid Carcinoma: A Comprehensive Clinical, Histologic, Immunophenotypic, and Molecular Study of 360 Cases","volume":"30","author":"Xu","year":"2020","journal-title":"Thyroid"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1056\/NEJMoa2309719","article-title":"Phase 3 Trial of Selpercatinib in Advanced RET -Mutant Medullary Thyroid Cancer","volume":"389","author":"Hadoux","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S2213-8587(21)00120-0","article-title":"Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): A multi-cohort, open-label, registrational, phase 1\/2 study","volume":"9","author":"Subbiah","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.jtho.2020.01.006","article-title":"RET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven Malignancies","volume":"15","author":"Solomon","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.annonc.2020.10.599","article-title":"Structural basis of acquired resistance to selpercatinib and pralsetinib mediated by non-gatekeeper RET mutations","volume":"32","author":"Subbiah","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1200\/JCO.2011.35.5040","article-title":"Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial","volume":"30","author":"Wells","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1200\/JCO.2012.48.4659","article-title":"Cabozantinib in Progressive Medullary Thyroid Cancer","volume":"31","author":"Elisei","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(14)60421-9","article-title":"Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: A randomised, double-blind, phase 3 trial","volume":"384","author":"Brose","year":"2014","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1056\/NEJMoa1406470","article-title":"Lenvatinib versus Placebo in Radioiodine-Refractory Thyroid Cancer","volume":"372","author":"Schlumberger","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/S1470-2045(21)00332-6","article-title":"Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"22","author":"Brose","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S1470-2045(19)30691-6","article-title":"Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: Integrated analysis of three phase 1\u20132 trials","volume":"21","author":"Doebele","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1210\/jc.2017-01613","article-title":"Increased Global DNA Hypomethylation in Distant Metastatic and Dedifferentiated Thyroid Cancer","volume":"103","author":"Hesselink","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_59","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_60","first-page":"215","article-title":"Targeting EZH2 reverses thyroid cell dedifferentiation and enhances iodide uptake in anaplastic thyroid cancer","volume":"600","author":"Henrique","year":"2025","journal-title":"FEBS Lett."},{"key":"ref_61","first-page":"1","article-title":"Integrative proteogenomic characterization reveals therapeutic targets in poorly differentiated and anaplastic thyroid cancers","volume":"16","author":"Pan","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-024-47581-1","article-title":"Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks","volume":"15","author":"Qu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Corver, W.E., Ruano, D., Weijers, K., Hartog, W.C.E.D., van Nieuwenhuizen, M.P., de Miranda, N., van Eijk, R., Middeldorp, A., Jordanova, E.S., and Oosting, J. (2012). Genome Haploidisation with Chromosome 7 Retention in Oncocytic Follicular Thyroid Carcinoma. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038287"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Chou, C.-K., Liu, R.-T., and Kang, H.-Y. (2017). MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030636"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1677\/ERC-07-0129","article-title":"MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle","volume":"14","author":"Visone","year":"2007","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_66","first-page":"881","article-title":"Role of extracellular vesicles in the progression, diagnosis and treatment of thyroid cancer (Review)","volume":"57","author":"Lu","year":"2020","journal-title":"Int. J. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12731","DOI":"10.18632\/oncotarget.7262","article-title":"miR-451a is underexpressed and targets AKT\/mTOR pathway in papillary thyroid carcinoma","volume":"7","author":"Minna","year":"2016","journal-title":"Oncotarget"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1089\/hum.2018.109","article-title":"LncRNA HOXA-AS2 Facilitates Tumorigenesis and Progression of Papillary Thyroid Cancer by Modulating the miR-15a-5p\/HOXA3 Axis","volume":"30","author":"Jiang","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1038\/s41418-023-01157-6","article-title":"LncRNA GLTC targets LDHA for succinylation and enzymatic activity to promote progression and radioiodine resistance in papillary thyroid cancer","volume":"30","author":"Shi","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12935-022-02817-2","article-title":"LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1","volume":"22","author":"Kuo","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-018-0382-7","article-title":"LncRNA HCP5 promotes follicular thyroid carcinoma progression via miRNAs sponge","volume":"9","author":"Liang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"110155","DOI":"10.1016\/j.cellsig.2021.110155","article-title":"Circ_0011058 facilitates proliferation, angiogenesis and radioresistance in papillary thyroid cancer cells by positively regulating YAP1 via acting as miR-335-5p sponge","volume":"88","author":"Zhang","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.21037\/gs-21-481","article-title":"Upregulated circRAD18 promotes tumor progression by reprogramming glucose metabolism in papillary thyroid cancer","volume":"10","author":"Chen","year":"2021","journal-title":"Gland. Surg."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Jaume, J.C. (2025). Thyroid Cancer\u2014The Tumor Immune Microenvironment (TIME) over Time and Space. Cancers, 17.","DOI":"10.3390\/cancers17050794"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5812","DOI":"10.62347\/QUWQ3794","article-title":"Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer","volume":"14","author":"Kimura","year":"2024","journal-title":"Am. J. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1089\/thy.2018.0555","article-title":"Targeting CD47 in Anaplastic Thyroid Carcinoma Enhances Tumor Phagocytosis by Macrophages and Is a Promising Therapeutic Strategy","volume":"29","author":"Roelli","year":"2019","journal-title":"Thyroid"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1158\/2767-9764.CRC-23-0120","article-title":"Characterizing the Immune Microenvironment and Neoantigen Landscape of H\u00fcrthle Cell Carcinoma to Identify Potential Immunologic Vulnerabilities","volume":"3","author":"Ganly","year":"2023","journal-title":"Cancer Res. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e250026","DOI":"10.1530\/EO-25-0026","article-title":"Macrophage abundance in oncocytic thyroid cancer is associated with PD-L1 expression","volume":"5","author":"Isaza","year":"2025","journal-title":"Endocr. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lu, L., Wang, J.R., Henderson, Y.C., Bai, S., Yang, J., Hu, M., Shiau, C.-K., Pan, T., Yan, Y., and Tran, T.M. (2023). Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics. J. Clin. Investig., 133.","DOI":"10.1172\/JCI169653"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-021-26343-3","article-title":"Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma","volume":"12","author":"Pu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s12020-018-1831-x","article-title":"Dysbiosis of the gut microbiome is associated with thyroid cancer and thyroid nodules and correlated with clinical index of thyroid function","volume":"64","author":"Zhang","year":"2018","journal-title":"Endocrine"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jare.2021.04.001","article-title":"Gut microbiota changes and its potential relations with thyroid carcinoma","volume":"35","author":"Yu","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s11154-023-09839-9","article-title":"The relationship between thyroid and human-associated microbiota: A systematic review of reviews","volume":"25","author":"Virili","year":"2023","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Lin, B., Zhao, F., Liu, Y., Sun, J., Feng, J., Zhao, L., Wang, H., Chen, H., Yan, W., and Guo, X. (2022). Alterations in Oral Microbiota of Differentiated Thyroid Carcinoma Patients With Xerostomia After Radioiodine Therapy. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.895970"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"100716","DOI":"10.1016\/j.ejro.2025.100716","article-title":"Machine Learning for diagnosis of malignant thyroid nodules based on thyroid ultrasound: Systematic review and meta-analysis of studies with external datasets","volume":"16","author":"Gatta","year":"2025","journal-title":"Eur. J. Radiol. Open"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-025-59478-8","article-title":"Improving AI models for rare thyroid cancer subtype by text guided diffusion models","volume":"16","author":"Dai","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6509","DOI":"10.1038\/s41598-026-37496-w","article-title":"Thyroid cancer detection and classification using spectral imaging and artificial intelligence","volume":"16","author":"Almagor","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41746-025-01652-9","article-title":"Multimodal GPT model for assisting thyroid nodule diagnosis and management","volume":"8","author":"Yao","year":"2025","journal-title":"npj Digit. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-025-62042-z","article-title":"Explainable multimodal deep learning for predicting thyroid cancer lateral lymph node metastasis using ultrasound imaging","volume":"16","author":"Shen","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41467-025-67533-7","article-title":"Multi-center multi-omics integration predicts individualized prognosis in medullary thyroid carcinoma","volume":"17","author":"Zhou","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"205","DOI":"10.32074\/1591-951X-887","article-title":"Molecular testing in indeterminate thyroid nodules: An additional tool for clinical decision-making","volume":"115","author":"Fumagalli","year":"2023","journal-title":"Pathologica"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Concepci\u00f3n-Zavaleta, M.J., Fuentes-Mendoza, J.M., Rojas-Hip\u00f3lito, C.A., S\u00e1nchez-Mej\u00eda, D., L\u00f3pez-Torres, M.A., Concepci\u00f3n-Urteaga, L., Armas, C.D., and Paz-Ibarra, J. (2026). Precision medicine in thyroid nodules: Current strategies, challenges, and future directions. Hormones.","DOI":"10.1007\/s42000-026-00757-4"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s12020-023-03610-5","article-title":"Improved guidance is needed to optimise diagnostics and treatment of patients with thyroid cancer in Europe","volume":"83","author":"Fugazzola","year":"2023","journal-title":"Endocrine"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.annonc.2020.11.021","article-title":"ESMO recommendations on the standard methods to detect RET fusions and mutations in daily practice and clinical research","volume":"32","author":"Belli","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Horgan, D., F\u00fchrer-Sakel, D., Soares, P., Alvarez, C.V., Fugazzola, L., Netea-Maier, R.T., Jarzab, B., Kozaric, M., Bartes, B., and Schuster-Bruce, J. (2022). Tackling Thyroid Cancer in Europe\u2014The Challenges and Opportunities. Healthcare, 10.","DOI":"10.3390\/healthcare10091621"},{"key":"ref_96","first-page":"1","article-title":"All models are wrong and yours are useless: Making clinical prediction models impactful for patients","volume":"8","author":"Markowetz","year":"2024","journal-title":"npj Precis. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7464\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:22:35Z","timestamp":1787372555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":96,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167464"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167464","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}