Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Sterlinga 3, 91-425 Lodz, Poland.
Clinic of Endocrinological and General Surgery, Chair of Endocrinology, Medical University of Lodz, Pabianicka 62, 93-513 Lodz, Poland.
Cytokine. 2018 May;105:32-36. doi: 10.1016/j.cyto.2018.02.013. Epub 2018 Feb 10.
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.
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.
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.
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.
βKlotho(βKL)已知作为成纤维细胞生长因子受体 4(FGFR4)的共受体起作用,FGFR4 是成纤维细胞生长因子 19(FGF19)的主要同源受体。该 FGF19/FGFR4/βKL 信号轴的失调已被认为与几种癌症的发病机制有关。然而,其在甲状腺癌发病机制中的作用尚未确定。
本研究的目的是评估一组 36 例甲状腺乳头状癌(PTC)、11 例滤泡性甲状腺癌(FTC)、9 例间变性甲状腺癌(ATC)患者和一组 19 例多结节非毒性甲状腺肿(MNG)患者的 FGF19、FGFR4 和 βKL 浓度。对照组由 20 名健康志愿者组成。使用特定的 ELISA 方法测量血清 FGF19、FGFR4 和 βKL 浓度。
与 MNG 组和对照组相比,PTC、FTC 和 ATC 患者的 βKL 浓度明显降低,FGF19 浓度升高。与 MNG 组和对照组相比,所有甲状腺癌组的 FGFR4 血清浓度均升高;然而,在 FTC 组,其差异无统计学意义。在 PTC 患者中发现 βKL 和 FGFR4 浓度之间存在正相关。MNG 组和健康对照组之间 βKL、FGF19 和 FGFR4 的水平无显著差异。
我们的结果表明,破坏的 FGF19/FGFR4/βKL 信号通路可能在甲状腺癌的发展中起作用。然而,需要进一步的研究来阐明甲状腺上皮细胞肿瘤转化的分子机制。