{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:23:14Z","timestamp":1760149394729,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["SFRH\/BD\/137802\/2018","NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018","NORTE-01-0145-FEDER-072678"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cancer Research on Therapy Resistance: From Basic Mechanisms to Novel Targets","award":["SFRH\/BD\/137802\/2018","NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018","NORTE-01-0145-FEDER-072678"]}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund (ERDF)","doi-asserted-by":"publisher","award":["SFRH\/BD\/137802\/2018","NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018","NORTE-01-0145-FEDER-072678"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NORTE 2020","award":["SFRH\/BD\/137802\/2018","NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018","NORTE-01-0145-FEDER-072678"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Angiotensin-Converting Enzyme 2 (ACE2), Transmembrane Serine Protease 2 (TMPRSS2), and Furin were known to be key players in the SARS-CoV-2 infection, and the thyroid gland was revealed to be one of the relevant targets of the virus. Regardless of the viral infection, the expression of these molecules in the thyroid gland and their putative role in the neoplastic transformation of the thyrocytes has not been thoroughly explored. In this work, we aimed to characterize the mRNA and protein expression pattern of ACE2, TMPRSS2, and Furin in a series of patients with thyroid lesions. Our main results revealed a significantly decreased expression of ACE2 mRNA in the thyroid neoplasms in comparison to normal adjacent tissue. Furin mRNA was significantly increased in thyroid neoplasms when compared to normal adjacent tissue. In addition, a higher Furin mRNA level in thyroid carcinomas was associated with the presence of lymph node metastasis. Furin mRNA expression revealed a high discriminatory power between adjacent tissue and neoplasms. Protein expression of these molecules did not correlate with mRNA expression. Our study shows the mRNA downregulation of ACE2 and overexpression of Furin in thyroid neoplasms. Further studies are required to clarify if Furin expression can be a potential diagnostic indicator in thyroid neoplasia.<\/jats:p>","DOI":"10.3390\/cancers15153909","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T09:24:24Z","timestamp":1690881864000},"page":"3909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Significance of Furin Expression in Thyroid Neoplastic Transformation"],"prefix":"10.3390","volume":"15","author":[{"given":"Maria Teresa","family":"Azevedo","sequence":"first","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Department of Pathology and Oncology, Faculty of Medicine, University of Porto (FMUP), 4200-139 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7752-998X","authenticated-orcid":false,"given":"Sofia","family":"Macedo","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Department of Pathology and Oncology, Faculty of Medicine, University of Porto (FMUP), 4200-139 Porto, Portugal"},{"name":"Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-1323","authenticated-orcid":false,"given":"Sule","family":"Canberk","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Department of Pathology and Oncology, Faculty of Medicine, University of Porto (FMUP), 4200-139 Porto, Portugal"},{"name":"Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Lu\u00eds","family":"Cardoso","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Department of Endocrinology, Diabetes and Metabolism, Coimbra Hospital and University Center, 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-7869","authenticated-orcid":false,"given":"Tiago Bordeira","family":"Gaspar","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Department of Pathology and Oncology, Faculty of Medicine, University of Porto (FMUP), 4200-139 Porto, Portugal"},{"name":"Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Ana","family":"Pestana","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Comprehensive Cancer Center, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}]},{"given":"Rui","family":"Batista","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal"}]},{"given":"Manuel","family":"Sobrinho-Sim\u00f5es","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Department of Pathology and Oncology, Faculty of Medicine, University of Porto (FMUP), 4200-139 Porto, Portugal"},{"name":"Department of Pathology, Centro Hospitalar de S\u00e3o Jo\u00e3o, 4200-139 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9607-6998","authenticated-orcid":false,"given":"Paula","family":"Soares","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Department of Pathology and Oncology, Faculty of Medicine, University of Porto (FMUP), 4200-139 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 Entry into Cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e220074","DOI":"10.1530\/ETJ-22-0074","article-title":"Detection of SARS-CoV-2 Infection in Thyroid Follicular Cells from a COVID-19 Autopsy Series","volume":"11","author":"Macedo","year":"2022","journal-title":"Eur. Thyroid. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/01.RES.87.5.e1","article-title":"A Novel Angiotensin-Converting Enzyme-Related Carboxypeptidase (Ace2) Converts Angiotensin I to Angiotensin 1-9","volume":"87","author":"Donoghue","year":"2000","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33238","DOI":"10.1074\/jbc.M002615200","article-title":"A Human Homolog of Angiotensin-Converting Enzyme. Cloning and Functional Expression as a Captopril-Insensitive Carboxypeptidase","volume":"275","author":"Tipnis","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s10096-020-04138-6","article-title":"COVID-19: Angiotensin-Converting Enzyme 2 (Ace2) Expression and Tissue Susceptibility to SARS-CoV-2 Infection","volume":"40","author":"Beyerstedt","year":"2021","journal-title":"Eur. J. Clin. Microbiol. Infect Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"BSR20202014","DOI":"10.1042\/BSR20202014","article-title":"Ace\/Ace2 Balance Might Be Instrumental to Explain the Certain Comorbidities Leading to Severe COVID-19 Cases","volume":"41","author":"Bank","year":"2021","journal-title":"Biosci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13045-020-00883-5","article-title":"Genetic Alteration, Rna Expression, and DNA Methylation Profiling of Coronavirus Disease 2019 (COVID-19) Receptor Ace2 in Malignancies: A Pan-Cancer Analysis","volume":"13","author":"Chai","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"481","DOI":"10.21037\/atm.2020.03.61","article-title":"A Profiling Analysis on the Receptor Ace2 Expression Reveals the Potential Risk of Different Type of Cancers Vulnerable to SARS-CoV-2 Infection","volume":"8","author":"Dai","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1515\/med-2020-0208","article-title":"Evaluation of COVID-19 Based on Ace2 Expression in Normal and Cancer Patients","volume":"15","author":"Ren","year":"2020","journal-title":"Open Med."},{"key":"ref_10","unstructured":"(2023, May 20). Human Protein Atlas. Available online: https:\/\/www.proteinatlas.org\/."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-Based Map of the Human Proteome","volume":"347","author":"Fagerberg","year":"2015","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1021\/cr000033x","article-title":"Serine Protease Mechanism and Specificity","volume":"102","author":"Lizbeth","year":"2002","journal-title":"Chem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1038\/bjc.2011.432","article-title":"Overexpression of Tmprss4 in Non-Small Cell Lung Cancer Is Associated with Poor Prognosis in Patients with Squamous Histology","volume":"105","author":"Larzabal","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1158\/0008-5472.CAN-14-3297","article-title":"Androgen-Induced Tmprss2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis","volume":"75","author":"Ko","year":"2015","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41589-022-01059-7","article-title":"Structure and Activity of Human Tmprss2 Protease Implicated in SARS-CoV-2 Activation","volume":"18","author":"Fraser","year":"2022","journal-title":"Nat. Chem. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.molmed.2009.05.003","article-title":"Type Ii Transmembrane Serine Proteases in Cancer and Viral Infections","volume":"15","author":"Choi","year":"2009","journal-title":"Trends Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1158\/2159-8290.CD-13-1010","article-title":"The Androgen-Regulated Protease Tmprss2 Activates a Proteolytic Cascade Involving Components of the Tumor Microenvironment and Promotes Prostate Cancer Metastasis","volume":"4","author":"Lucas","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/path.2330","article-title":"The Androgen-Regulated Type Ii Serine Protease Tmprss2 Is Differentially Expressed and Mislocalized in Prostate Adenocarcinoma","volume":"215","author":"Lucas","year":"2008","journal-title":"J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.2353\/ajpath.2010.090665","article-title":"Tmprss2, a Serine Protease Expressed in the Prostate on the Apical Surface of Luminal Epithelial Cells and Released into Semen in Prostasomes, Is Misregulated in Prostate Cancer Cells","volume":"176","author":"Chen","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1016\/j.mayocp.2020.06.018","article-title":"Targeting Tmprss2 in SARS-CoV-2 Infection","volume":"95","author":"Baughn","year":"2020","journal-title":"Mayo. Clin. Proc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101615","DOI":"10.1016\/j.redox.2020.101615","article-title":"Expression Profiling Meta-Analysis of Ace2 and Tmprss2, the Putative Anti-Inflammatory Receptor and Priming Protease of SARS-CoV-2 in Human Cells, and Identification of Putative Modulators","volume":"36","author":"Gkogkou","year":"2020","journal-title":"Redox Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s10096-020-04089-y","article-title":"Expression and Co-Expression Analyses of Tmprss2, a Key Element in COVID-19","volume":"40","author":"Piva","year":"2021","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101744","DOI":"10.1016\/j.isci.2020.101744","article-title":"SARS-CoV-2 Targets by the Pscrna Profiling of Ace2, Tmprss2 and Furin Proteases","volume":"23","author":"Zhou","year":"2020","journal-title":"iScience"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"648402","DOI":"10.3389\/fmolb.2021.648402","article-title":"Pan-Cancer Analysis of Furin as a Potential Prognostic and Immunological Biomarker","volume":"8","author":"Zhou","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/bj3270625","article-title":"Furin: A Mammalian Subtilisin\/Kex2p-Like Endoprotease Involved in Processing of a Wide Variety of Precursor Proteins","volume":"327","author":"Nakayama","year":"1997","journal-title":"Biochem. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nrd3699","article-title":"The Biology and Therapeutic Targeting of the Proprotein Convertases","volume":"11","author":"Seidah","year":"2012","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12127","DOI":"10.1016\/S0021-9258(18)98867-8","article-title":"Arg-X-Lys\/Arg-Arg Motif as a Signal for Precursor Cleavage Catalyzed by Furin within the Constitutive Secretory Pathway","volume":"266","author":"Hosaka","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16396","DOI":"10.1016\/S0021-9258(18)42016-9","article-title":"Human Furin Is a Calcium-Dependent Serine Endoprotease That Recognizes the Sequence Arg-X-X-Arg and Efficiently Cleaves Anthrax Toxin Protective Antigen","volume":"267","author":"Molloy","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.3892\/or.2016.4967","article-title":"Ace2 Overexpression Inhibits Acquired Platinum Resistance-Induced Tumor Angiogenesis in Nsclc","volume":"36","author":"Cheng","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/mc.1057","article-title":"Elevated Furin Expression in Aggressive Human Head and Neck Tumors and Tumor Cell Lines","volume":"31","author":"Bassi","year":"2001","journal-title":"Mol. Carcinog."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1172\/JCI113240","article-title":"Fur Gene Expression as a Discriminating Marker for Small Cell and Nonsmall Cell Lung Carcinomas","volume":"80","author":"Schalken","year":"1987","journal-title":"J. Clin. Invest."},{"key":"ref_32","first-page":"289","article-title":"Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer","volume":"29","author":"Page","year":"2007","journal-title":"Cell Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3954","DOI":"10.7150\/ijbs.63072","article-title":"COVID-19 Disease and Malignant Cancers: The Impact for the Furin Gene Expression in Susceptibility to SARS-CoV-2","volume":"17","author":"Li","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13396","DOI":"10.1002\/1878-0261.13396","article-title":"Overexpression of the Pro-Protein Convertase Furin Predicts Prognosis and Promotes Papillary Thyroid Carcinoma Progression and Metastasis through Raf\/Mek Signaling","volume":"17","author":"Poyil","year":"2023","journal-title":"Mol. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1002\/ijc.30714","article-title":"The Proprotein Convertase Furin in Tumour Progression","volume":"141","author":"Jaaks","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pestana, A., Batista, R., Celestino, R., Canberk, S., Sobrinho-Sim\u00f5es, M., and Soares, P. (2020). Comprehensive Assessment of Tert Mrna Expression across a Large Cohort of Benign and Malignant Thyroid Tumours. Cancers, 12.","DOI":"10.3390\/cancers12071846"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13000-014-0221-9","article-title":"Different Approaches for Interpretation and Reporting of Immunohistochemistry Analysis Results in the Bone Tissue-a Review","volume":"9","author":"Fedchenko","year":"2014","journal-title":"Diagn. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.21105\/joss.03021","article-title":"Seaborn: Statistical Data Visualization","volume":"6","author":"Waskom","year":"2021","journal-title":"J. Open Source Softw."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1089\/thy.2017.0102","article-title":"Updated American Joint Committee on Cancer\/Tumor-Node-Metastasis Staging System for Differentiated and Anaplastic Thyroid Cancer (Eighth Edition): What Changed and Why?","volume":"27","author":"Tuttle","year":"2017","journal-title":"Thyroid"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s40249-020-00662-x","article-title":"Expression of the SARS-CoV-2 Cell Receptor Gene Ace2 in a Wide Variety of Human Tissues","volume":"9","author":"Li","year":"2020","journal-title":"Infect. Dis. Poverty"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.7150\/ijms.46695","article-title":"A Comprehensive Investigation of the Mrna and Protein Level of Ace2, the Putative Receptor of SARS-CoV-2, in Human Tissues and Blood Cells","volume":"17","author":"Wang","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"109583","DOI":"10.1016\/j.cbi.2021.109583","article-title":"Computational Analysis of Tmprss2 Expression in Normal and SARS-CoV-2-Infected Human Tissues","volume":"346","author":"Cao","year":"2021","journal-title":"Chem. Biol. Interact."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e9610","DOI":"10.15252\/msb.20209610","article-title":"The Protein Expression Profile of Ace2 in Human Tissues","volume":"16","author":"Hikmet","year":"2020","journal-title":"Mol. Syst Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on Ace2 and Tmprss2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Park, G.-C., Lee, H.-W., Kim, J.-M., Han, J.-M., Kim, H.-I., Shin, S.-C., Cheon, Y.-I., Sung, E.-S., Lee, M., and Lee, J.-C. (2022). Ace2 and Tmprss2 Immunolocalization and COVID-19-Related Thyroid Disorder. Biology, 11.","DOI":"10.3390\/biology11050697"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s40618-020-01436-w","article-title":"Detection of SARS-CoV-2 Receptor Ace-2 Mrna in Thyroid Cells: A Clue for COVID-19-Related Subacute Thyroiditis","volume":"44","author":"Rotondi","year":"2021","journal-title":"J. Endocrinol. Invest."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s11154-020-09615-z","article-title":"Impact of COVID-19 on the Thyroid Gland: An Update","volume":"22","author":"Scappaticcio","year":"2021","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1136\/jitc-2020-001020","article-title":"Ace2 and Tmprss2 Expression by Clinical, Hla, Immune, and Microbial Correlates across 34 Human Cancers and Matched Normal Tissues: Implications for SARS-CoV-2 COVID-19","volume":"8","author":"Bao","year":"2020","journal-title":"J. Immunother Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"402","DOI":"10.4149\/neo_2019_190506N405","article-title":"Angiotensin Converting Enzymes Ace and Ace2 in Thyroid Cancer Progression","volume":"67","author":"Narayan","year":"2020","journal-title":"Neoplasma"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s13046-019-1156-5","article-title":"Ace2 Inhibits Breast Cancer Angiogenesis Via Suppressing the Vegfa\/Vegfr2\/Erk Pathway","volume":"38","author":"Zhang","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8847307","DOI":"10.1155\/2021\/8847307","article-title":"Ace2 Is a Prognostic Biomarker and Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma: Implication for COVID-19","volume":"2021","author":"Niu","year":"2021","journal-title":"J. Oncol."},{"key":"ref_52","first-page":"1483","article-title":"Human Telomerase Reverse Transcriptase (Htert) Gene Expression in Thyroid Neoplasms","volume":"5","author":"Saji","year":"1999","journal-title":"Clin. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41368-020-0074-x","article-title":"High Expression of Ace2 Receptor of 2019-Ncov on the Epithelial Cells of Oral Mucosa","volume":"12","author":"Xu","year":"2020","journal-title":"Int. J. Oral Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1164\/rccm.202001-0179LE","article-title":"Single-Cell Rna Expression Profiling of Ace2, the Receptor of SARS-CoV-2","volume":"202","author":"Hao","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1007\/s00134-020-05985-9","article-title":"Angiotensin-Converting Enzyme 2 (Ace2) as a SARS-CoV-2 Receptor: Molecular Mechanisms and Potential Therapeutic Target","volume":"46","author":"Zhang","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1007\/s12020-021-02807-w","article-title":"Modulation of Ace-2 Mrna by Inflammatory Cytokines in Human Thyroid Cells: A Pilot Study","volume":"74","author":"Coperchini","year":"2021","journal-title":"Endocrine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"bqaa108","DOI":"10.1210\/endocr\/bqaa108","article-title":"Endocrine Significance of SARS-CoV-2\u2019s Reliance on Ace2","volume":"161","author":"Lazartigues","year":"2020","journal-title":"Endocrinology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"647826","DOI":"10.3389\/fmolb.2022.647826","article-title":"Tmprss2 Serves as a Prognostic Biomarker and Correlated with Immune Infiltrates in Breast Invasive Cancer and Lung Adenocarcinoma","volume":"9","author":"Xiao","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41586-022-04474-x","article-title":"Altered Tmprss2 Usage by SARS-CoV-2 Omicron Impacts Infectivity and Fusogenicity","volume":"603","author":"Meng","year":"2022","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"963689720968749","DOI":"10.1177\/0963689720968749","article-title":"Ace2 and Tmprss2 Potential Involvement in Genetic Susceptibility to SARS-CoV-2 in Cancer Patients","volume":"29","author":"Ravaioli","year":"2020","journal-title":"Cell Transpl."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1089\/thy.2012.0269","article-title":"Multivariate Analysis of the Relationship between Male Sex, Disease-Specific Survival, and Features of Tumor Aggressiveness in Thyroid Cancer of Follicular Cell Origin","volume":"23","author":"Nilubol","year":"2013","journal-title":"Thyroid"},{"key":"ref_62","first-page":"2763","article-title":"Tert Promoter Mutations and Their Correlation with Braf and Ras Mutations in a Consecutive Cohort of 145 Thyroid Cancer Cases","volume":"15","author":"Insilla","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Xing, M. (2016). Clinical Utility of Ras Mutations in Thyroid Cancer: A Blurred Picture Now Emerging Clearer. BMC Med., 14.","DOI":"10.1186\/s12916-016-0559-9"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ricardo, S., Can\u00e3o, P., Martins, D., Magalh\u00e3es, A.C., Pereira, M., Ribeiro-Junior, U., de Mello, E.S., Alves, V.A., Pinto, R., and Leit\u00e3o, D. (2022). Searching for SARS-CoV-2 in Cancer Tissues: Results of an Extensive Methodologic Approach Based on Ace2 and Furin Expression. Cancers, 14.","DOI":"10.3390\/cancers14112582"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.compbiolchem.2008.07.014","article-title":"Discrepancy between Mrna and Protein Abundance: Insight from Information Retrieval Process in Computers","volume":"32","author":"Wang","year":"2008","journal-title":"Comput. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"lqz010","DOI":"10.1093\/nargab\/lqz010","article-title":"Global Variability Analysis of Mrna and Protein Concentrations across and within Human Tissues","volume":"2","author":"Wegler","year":"2020","journal-title":"NAR Genom. Bioinform."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/15\/3909\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:23:41Z","timestamp":1760127821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/15\/3909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,1]]},"references-count":66,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["cancers15153909"],"URL":"https:\/\/doi.org\/10.3390\/cancers15153909","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2023,8,1]]}}}