Ewelina Motylewska1, Tomasz Stępień2, Magdalena Borkowska2, Krzysztof Kuzdak2, Agnieszka Siejka3, Jan Komorowski3, Henryk Stępień4, Hanna Ławnicka4. 1. Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Sterlinga 3, 91-425 Lodz, Poland. Electronic address: ewelina.motylewska@umed.lodz.pl. 2. Clinic of Endocrinological and General Surgery, Chair of Endocrinology, Medical University of Lodz, Pabianicka 62, 93-513 Lodz, Poland. 3. Clinic of Endocrinology, Chair of Endocrinology, Medical University of Lodz, Sterlinga 3, 91-425 Lodz, Poland. 4. Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Sterlinga 3, 91-425 Lodz, Poland.
Abstract
INTRODUCTION: βKlotho (βKL) is known to act as co-receptor for fibroblast growth factor receptor 4 (FGFR4) which is the main cognate receptor for fibroblast growth factor 19 (FGF19). Dysregulation of this FGF19/FGFR4/βKL signaling axis has been implicated in the pathogenesis of several cancers. However, its role in the pathogenesis of thyroid cancer has not been determined. MATERIALS AND METHODS: The aim of this study was to assess FGF19, FGFR4 and βKL concentrations in a group of 36 patients with papillary thyroid cancer (PTC), 11 patients with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and a group of 19 subjects with multinodular nontoxic goiter (MNG). The control group consisted of 20 healthy volunteers. Serum FGF19, FGFR4 and βKL concentrations were measured using specific ELISA methods. RESULTS: Significantly lower concentrations of βKL and higher concentrations of FGF19 were found in patients with PTC, FTC and ATC as compared with MNG group and controls. An elevation of FGFR4 serum concentration was observed in all thyroid cancer groups in comparison to MNG group and controls; however, in FTC group it was statistically insignificant. A positive correlation was found between βKL and FGFR4 concentrations in PTC patients. The levels of βKL, FGF19 and FGFR4 did not differ significantly between MNG group and healthy controls. CONCLUSIONS: Our results indicate that a disrupted FGF19/FGFR4/βKL signaling pathway may play a role in the development of thyroid cancers. However, further studies are needed to elucidate the molecular mechanism of the neoplastic transition of thyroid epithelial cells.
INTRODUCTION: βKlotho (βKL) is known to act as co-receptor for fibroblast growth factor receptor 4 (FGFR4) which is the main cognate receptor for fibroblast growth factor 19 (FGF19). Dysregulation of this FGF19/FGFR4/βKL signaling axis has been implicated in the pathogenesis of several cancers. However, its role in the pathogenesis of thyroid cancer has not been determined. MATERIALS AND METHODS: The aim of this study was to assess FGF19, FGFR4 and βKL concentrations in a group of 36 patients with papillary thyroid cancer (PTC), 11 patients with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and a group of 19 subjects with multinodular nontoxic goiter (MNG). The control group consisted of 20 healthy volunteers. Serum FGF19, FGFR4 and βKL concentrations were measured using specific ELISA methods. RESULTS: Significantly lower concentrations of βKL and higher concentrations of FGF19 were found in patients with PTC, FTC and ATC as compared with MNG group and controls. An elevation of FGFR4 serum concentration was observed in all thyroid cancer groups in comparison to MNG group and controls; however, in FTC group it was statistically insignificant. A positive correlation was found between βKL and FGFR4 concentrations in PTC patients. The levels of βKL, FGF19 and FGFR4 did not differ significantly between MNG group and healthy controls. CONCLUSIONS: Our results indicate that a disrupted FGF19/FGFR4/βKL signaling pathway may play a role in the development of thyroid cancers. However, further studies are needed to elucidate the molecular mechanism of the neoplastic transition of thyroid epithelial cells.
Authors: Andrew Thompson; James Cook; Hélène Choquet; Eric Jorgenson; Jie Yin; Tarja Kinnunen; Jeff Barclay; Andrew P Morris; Munir Pirmohamed Journal: Sci Adv Date: 2020-01-15 Impact factor: 14.136