{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:19:11Z","timestamp":1791505151473,"version":"4.3.4"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012952","name":"Universit\u00e9 Grenoble Alpes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012952","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Thyroid cancer is the most common endocrine cancer. There is no systematic screening for such cancer, and the current challenge is to find potential biomarkers to facilitate an early diagnosis. Copper (Cu) and zinc (Zn) are essential micronutrients involved in the proper functioning of the thyroid gland, and changes in their concentrations have been observed in the development of cancer. Previous studies have highlighted the potential <jats:sup>65<\/jats:sup>Cu\/<jats:sup>63<\/jats:sup>Cu ratio (\u03b4<jats:sup>65<\/jats:sup>Cu) to be a cancer biomarker. This study tests its sensitivity on plasma samples (<jats:italic>n<\/jats:italic> = 46) of Algerian patients with papillary thyroid carcinoma and a set of corresponding biopsies (<jats:italic>n<\/jats:italic> = 11). The \u03b4<jats:sup>65<\/jats:sup>Cu ratio in blood and tumor samples was determined using multi collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), and their corresponding Cu and Zn plasma total concentrations using total reflection X-ray fluorescence (TXRF). Plasma concentrations of Cu were significantly higher (1346.1 \u00b1 328.3 vs. 1060.5 \u00b1 216.1 \u03bcg\/L, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), and Zn significantly lower (942.1 \u00b1 205.2 vs. 1027.9 \u00b1 151.4 \u03bcg\/L, <jats:italic>p<\/jats:italic> &amp;lt; 0.05) in thyroid cancer patients as compared to healthy controls (<jats:italic>n<\/jats:italic> = 50). Accordingly, the Cu\/Zn ratio was significantly different between patients and controls (1.5 \u00b1 0.4 vs. 1.0 \u00b1 0.3, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001). Furthermore, the \u03b4<jats:sup>65<\/jats:sup>Cu plasma levels of patients were significantly lower than healthy controls (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001), whereas thyroid tumor tissues presented high \u03b4<jats:sup>65<\/jats:sup>Cu values. These results support the hypothesis that Cu isotopes and plasma trace elements may serve as suitable biomarkers of thyroid cancer diagnosis.<\/jats:p>","DOI":"10.3389\/fmed.2021.698167","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T04:26:47Z","timestamp":1631075207000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":47,"title":["Copper Isotopes and Copper to Zinc Ratio as Possible Biomarkers for Thyroid Cancer"],"prefix":"10.3389","volume":"8","author":[{"given":"Latifa Sarra","family":"Kazi Tani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra T.","family":"Gourlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouria","family":"Dennouni-Medjati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Telouk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majda","family":"Dali-Sahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahia","family":"Harek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Hackler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moussa","family":"Belhadj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Schomburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Charlet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"B1","first-page":"837","volume-title":"Cancer incidence in Five Continents Volume IX","author":"Curado","year":"2008"},{"key":"B2","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.rpedm.2016.04.003","article-title":"Molecular biology of papillary thyroid microcarcinomas: what is new?","volume":"11","author":"Castro","year":"2016","journal-title":"Endocrinol Diabetes E Metab."},{"key":"B3","unstructured":"ThyroidCancer\n          Cancer Stat Facts.2020"},{"key":"B4","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1080\/10408398.2020.1714542","article-title":"Nutritional status and follicular-derived thyroid cancer: an update","volume":"61","author":"Barrea","year":"2021","journal-title":"Crit Rev Food Sci Nutr."},{"key":"B5","unstructured":"IARCGLOBO-CAN 2018: Estimated Cancer Incidence, Mortality and Prevalence in Algeria in 20182019"},{"key":"B6","doi-asserted-by":"publisher","first-page":"672","DOI":"10.4236\/jct.2017.87058","article-title":"Thyroid cancer in Western Algeria: histopathological and epidemiological study","volume":"8","author":"Benouis","year":"2017","journal-title":"J Cancer Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2783","DOI":"10.1016\/S0140-6736(16)30172-6","article-title":"Thyroid cancer","volume":"388","author":"Cabanillas","year":"2016","journal-title":"Lancet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e0236257","DOI":"10.1371\/journal.pone.0236257","article-title":"Cancer screening activity results in overdiagnosis and overtreatment of papillary thyroid cancer: a 10-year experience at a single institution","volume":"15","author":"Kaliszewski","year":"2020","journal-title":"PLoS ONE."},{"key":"B9","first-page":"526","volume-title":"Biochemistry of Copper","author":"Linder","year":"2013"},{"key":"B10","doi-asserted-by":"publisher","first-page":"19507","DOI":"10.1073\/pnas.1318431110","article-title":"Bioavailable copper modulates oxidative phosphorylation and growth of tumors","volume":"110","author":"Ishida","year":"2013","journal-title":"Proc Natl Acad Sci USA."},{"key":"B11","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.ccr.2010.04.011","article-title":"Enhancing tumor-specific uptake of the anticancer drug cisplatin with a copper chelator","volume":"17","author":"Ishida","year":"2010","journal-title":"Cancer Cell."},{"key":"B12","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1039\/C4MT00269E","article-title":"Copper isotope effect in serum of cancer patients. 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