Copper Isotopes and Copper to Zinc Ratio as Possible Biomarkers for Thyroid Cancer.

Latifa Sarra Kazi Tani,Moussa Belhadj,Laurent Charlet,Qian Sun,Nouria Dennouni-Medjati,Philippe Telouk,Majda Dali-Sahi,Lutz Schomburg,Yahia Harek,Alexandra T Gourlan,Julian Hackler

doi:10.3389/fmed.2021.698167

Abstract

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 65Cu/63Cu ratio (δ65Cu) to be a cancer biomarker. This study tests its sensitivity on plasma samples (n = 46) of Algerian patients with papillary thyroid carcinoma and a set of corresponding biopsies (n = 11). The δ65Cu 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 ± 328.3 vs. 1060.5 ± 216.1 μg/L, p < 0.0001), and Zn significantly lower (942.1 ± 205.2 vs. 1027.9 ± 151.4 μg/L, p < 0.05) in thyroid cancer patients as compared to healthy controls (n = 50). Accordingly, the Cu/Zn ratio was significantly different between patients and controls (1.5 ± 0.4 vs. 1.0 ± 0.3, p < 0.0001). Furthermore, the δ65Cu plasma levels of patients were significantly lower than healthy controls (p < 0.0001), whereas thyroid tumor tissues presented high δ65Cu values. These results support the hypothesis that Cu isotopes and plasma trace elements may serve as suitable biomarkers of thyroid cancer diagnosis.

Highlights

Thyroid cancer is the most frequent malignancy of the endocrine system, responsible for almost 90% of endocrine cancers [1, 2], and accounting for the Surveillance, Epidemiology, and End Results (SEER) Stat Fact 4% of all new cancer cases in the US [3]
A value was considered as abnormal when it was outside the standard range: Thyroid Stimulating Hormone (TSH) 0.3 < TSH < 5.0 μIU/mL, anti-thyroid peroxidase antibodies (TPOab) < 34 UI/mL and thyroglobulin (TG) levels 3.0 < TG < 40 ng/mL
We observed that thyroid biomarkers are highly perturbed in the individuals with thyroid cancer compared to the international standard

Summary

Introduction

Thyroid cancer is the most frequent malignancy of the endocrine system, responsible for almost 90% of endocrine cancers [1, 2], and accounting for the Surveillance, Epidemiology, and End Results (SEER) Stat Fact 4% of all new cancer cases in the US [3]. Its incidence is increasing with 567.000 new cases annually, ranking it the 9th place worldwide. It is diagnosed three times more in woman (10.2 per 100,000) than in men (3.1 per 100,000) [4]. In Algeria, thyroid cancer incidence is increasing, taking the 3rd place in women after breast and colorectal cancer, Metal Isotopes Thyroid Cancer Biomarker while in 2006 it occupied the 5th position in frequency [5, 6]. There is no systematic detection of thyroid cancer, and the diagnosis is made incidentally in 25% of cases during the follow-up of another thyroid disease [2, 8]. A current challenge lies in identifying suitable biomarkers for supporting a fast diagnosis of thyroid cancer

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