{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T19:25:31Z","timestamp":1770492331098,"version":"3.49.0"},"reference-count":52,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/01796"],"award-info":[{"award-number":["PI17\/01796"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Acci\u00f3n Estrat\u00e9gica en Salud"},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AECC Foundation","award":["AIO15152858"],"award-info":[{"award-number":["AIO15152858"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The identification of markers able to determine medullary thyroid cancer (MTC) patients at high-risk of disease progression is critical to improve their clinical management and outcome. Previous studies have suggested that expression of the stem cell marker CD133 is associated with MTC aggressiveness.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To evaluate CD133 impact on disease progression in MTC and explore the regulatory mechanisms leading to the upregulation of this protein in aggressive tumors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>We compiled a series of 74 MTCs with associated clinical data and characterized them for mutations in RET and RAS proto-oncogenes, presumed to be related with disease clinical behavior.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found that CD133 immunohistochemical expression was associated with adverse clinicopathological features and predicted a reduction in time to disease progression even when only RET-mutated cases were considered in the analysis (log-rank test P\u2005&amp;lt;\u20050.003). Univariate analysis for progression-free survival revealed CD133 expression and presence of tumor emboli in peritumoral blood vessels as the most significant prognostic covariates among others such as age, gender, and prognostic stage. Multivariate analysis identified both variables as independent factors of poor prognosis (hazard ratio\u2005=\u200516.6 and 2; P\u2005=\u20050.001 and 0.010, respectively). Finally, we defined hsa-miR-30a-5p, a miRNA downregulated in aggressive MTCs, as a CD133 expression regulator. Ectopic expression of hsa-miR-30a-5p in MZ-CRC-1 (RETM918T) cells significantly reduced CD133 mRNA expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results suggest that CD133 expression may be a useful tool to identify MTC patients with poor prognosis, who may benefit from a more extensive primary surgical management and follow-up.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa527","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T05:29:47Z","timestamp":1597382987000},"page":"3548-3561","source":"Crossref","is-referenced-by-count":9,"title":["CD133 Expression in Medullary Thyroid Cancer Cells Identifies Patients with Poor Prognosis"],"prefix":"10.1210","volume":"105","author":[{"given":"Alfonso","family":"Cordero-Barreal","sequence":"first","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Caleiras","sequence":"additional","affiliation":[{"name":"Histopathology Core Unit, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangelina","family":"L\u00f3pez de Maturana","sequence":"additional","affiliation":[{"name":"Genetic & Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain"},{"name":"Basic Medical Sciences, Medical School, San Pablo-CEU University, Boadilla del Monte, Spain"},{"name":"Biomedical Research Networking Centre on Oncology (CIBERONC), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Monteagudo","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1ngel M","family":"Mart\u00ednez-Montes","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Let\u00f3n","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Gil","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"\u00c1lvarez-Escol\u00e1","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department and Pathological Anatomy Service, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita M","family":"Regojo","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department and Pathological Anatomy Service, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00edctor","family":"And\u00eda","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica","family":"Marazuela","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Universitario La Princesa, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonsoles","family":"Guadalix","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Calatayud","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Robles-D\u00edaz","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Ciudad Real, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juana M","family":"Cano","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Universitario de Ciudad Real, Ciudad Real, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 \u00c1ngel","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Cl\u00ednico San Carlos, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Saavedra","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Universitario Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Lamas","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Complejo Hospitalario Universitario de Albacete, Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharona","family":"Azriel","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Universitario Infanta Sof\u00eda, San Sebasti\u00e1n de los Reyes, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Sastre","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Virgen de la Salud, Toledo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Aller","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Universitario Puerta de Hierro, Majadahonda, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis J","family":"Leandro-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruna","family":"Calsina","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Mar\u00eda","family":"Rold\u00e1n-Romero","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Santos","sequence":"additional","affiliation":[{"name":"Hereditary 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Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Robledo","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Madrid, Spain"},{"name":"Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4452-4469","authenticated-orcid":false,"given":"Cristina","family":"Montero-Conde","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2020,8,13]]},"reference":[{"issue":"6","key":"2021122106120149100_CIT0001","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1089\/thy.2014.0335","article-title":"Revised American Thyroid Association guidelines for the management of medullary thyroid 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