Research Centre for Medical Genetics, Moscow, Russia.
Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia.
Endocrine. 2021 Jun;72(3):735-743. doi: 10.1007/s12020-020-02513-z. Epub 2020 Oct 3.
Cytochrome b5-reductase (CYB5R) and cytochrome P450 reductase (CYPOR) are important for cell metabolism; however, their role in thyroid hormonogenesis and carcinogenesis has not been elucidated yet. The activity of CYB5R correlates with the metastasis in breast cancer, but there are no similar studies for CYB5R and CYPOR for thyroid tumors. The aim of this study was to elucidate the activity of CYB5R and CYPOR changes in benign euthyroid and hyperthyroid neoplasms and in papillary thyroid cancer for their potential application as biomarkers for diagnosis and prognosis prediction of thyroid cancer.
Thirty-six patients with thyroid diseases participated in the study. The control euthyroid nodular goiter group included ten patients; the thyrotoxic nodular or diffuse goiter group included 14 patients; the papillary thyroid cancer T1-2N0-1M0 (PTC) group included 12 patients. The activity of CYB5R and CYPOR was assessed with lucigenin-enhanced chemiluminescence stimulated by NADH and NADPH, respectively.
Compared to the control euthyroid nodular goiter group, activity of CYB5R and CYPOR increased ~5 and 10 times, respectively, in toxic goiter, and 15 and 30 times, respectively, in half of cases of PTC. The change in activity of CYPOR was more pronounced compared to CYB5R. Within the PTC group, the subgroups with low and high activities of microsomal reductases were identified. Microsomal reductases in follicular adenoma was 2-4-fold less active compared to the euthyroid nodular goiter and the low-activity PTC group.
Activity of tissue microsomal reductases varies in thyroid pathology and can be considered as a promising biomarker for differential diagnostics of benign and malignant thyroid tumors.
细胞色素 b5 还原酶 (CYB5R) 和细胞色素 P450 还原酶 (CYPOR) 对细胞代谢很重要；然而，它们在甲状腺激素生成和癌变中的作用尚未阐明。CYB5R 的活性与乳腺癌的转移相关，但尚未有类似的研究探讨 CYB5R 和 CYPOR 在甲状腺肿瘤中的作用。本研究旨在阐明良性甲状腺功能正常和甲状腺功能亢进性肿瘤以及甲状腺乳头状癌中 CYB5R 和 CYPOR 活性的变化，以期将其作为甲状腺癌诊断和预后预测的潜在生物标志物。
36 例甲状腺疾病患者参与了本研究。对照组为甲状腺功能正常的结节性甲状腺肿患者，包括 10 例；甲状腺功能亢进性结节性或弥漫性甲状腺肿患者包括 14 例；甲状腺乳头状癌 T1-2N0-1M0（PTC）患者包括 12 例。使用 NADH 和 NADPH 刺激的鲁米诺增强化学发光法评估 CYB5R 和 CYPOR 的活性。
与对照组甲状腺功能正常的结节性甲状腺肿患者相比，毒性甲状腺肿患者的 CYB5R 和 CYPOR 活性分别增加了约 5 倍和 10 倍，而半数 PTC 患者的活性分别增加了 15 倍和 30 倍。与 CYB5R 相比，CYPOR 的活性变化更为明显。在 PTC 组中，发现了低和高活性的微粒体还原酶亚组。与甲状腺功能正常的结节性甲状腺肿和低活性 PTC 组相比，滤泡性腺瘤中的微粒体还原酶活性低 2-4 倍。
组织微粒体还原酶的活性在甲状腺病理中存在差异，可作为鉴别诊断良性和恶性甲状腺肿瘤的有前途的生物标志物。
