Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.
Endocrine Surgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy.
Front Endocrinol (Lausanne). 2021 Mar 29;12:647369. doi: 10.3389/fendo.2021.647369. eCollection 2021.
Having previously demonstrated that tissue miR-375 expression in medullary thyroid carcinoma (MTC) tissues is linked to prognosis, the aim of this study was to assess the diagnostic and prognostic value of circulating miR-375 levels in MTC patients.
A series of 68 patients with MTC was retrospectively retrieved and assessed in terms of their clinicopathological characteristics. MiR-375 levels were measured in all patients' presurgical blood samples. Both serum and tissue levels were tested prior to surgery in a subgroup of 57 patients. Serum miR-375 levels were also measured in serum from 49 patients with non-C-cell thyroid nodular diseases (non-CTN), 14 patients with pheochromocytoma, and 19 healthy controls.
Circulating miR-375 levels were 101 times higher in the serum of patients with MTC than in all other patients and controls, with no overlap (P < 0.01). No correlation emerged between serum and tissue miR-375 levels. Serum miR-375 levels were higher in MTC patients with N0 than in those with N1 disease (P = 0.01), and also in patients who were biochemically cured than in those who were not (P = 0.02). In the whole series of patients and controls, calcitonin (CT) and serum miR-375 levels were correlated at diagnosis (R = 0.40, P < 0.01), but in a U-shaped manner: a positive correlation was found with low CT levels, then the correlation turns negative as CT rises (in MTC patients). A negative correlation was indeed found in MTC patients between serum miR-375 and CT (R = -0.10, P = 0.01). On ROC curve analysis, a cut-off of 2.1 for serum miR-375 proved capable of distinguishing between MTC patients and the other patients and controls with a 92.6% sensitivity and a 97.6% specificity (AUC: 0.978, P < 0.01).
Serum miR-375 levels can serve as a marker in the diagnosis of MTC, with a remarkable specificity. Serum miR-375 also proved a novel marker of prognosis in this disease. Further experiments to corroborate our results are currently underway.
先前的研究表明，甲状腺髓样癌（MTC）组织中 miR-375 的表达与预后相关，本研究旨在评估 MTC 患者循环 miR-375 水平的诊断和预后价值。
回顾性检索了 68 例 MTC 患者，并评估了其临床病理特征。所有患者术前均采集血样检测 miR-375 水平。在 57 例患者中术前同时检测血清和组织 miR-375 水平。还检测了 49 例非 C 细胞甲状腺结节性疾病（非 CTN）患者、14 例嗜铬细胞瘤患者和 19 例健康对照者的血清 miR-375 水平。
MTC 患者血清中循环 miR-375 水平比所有其他患者和对照组高 101 倍，无重叠（P < 0.01）。血清和组织 miR-375 水平之间无相关性。N0 期 MTC 患者的血清 miR-375 水平高于 N1 期（P = 0.01），且生化治愈者高于未治愈者（P = 0.02）。在患者和对照组的整个系列中，降钙素（CT）和血清 miR-375 水平在诊断时呈正相关（R = 0.40，P < 0.01），但呈 U 型关系：与低 CT 水平呈正相关，然后随着 CT 升高而呈负相关（在 MTC 患者中）。MTC 患者的血清 miR-375 与 CT 之间确实存在负相关（R = -0.10，P = 0.01）。在 ROC 曲线分析中，血清 miR-375 的截断值为 2.1，可区分 MTC 患者与其他患者和对照组，其敏感性为 92.6%，特异性为 97.6%（AUC：0.978，P < 0.01）。
血清 miR-375 水平可作为 MTC 诊断的标志物，具有显著的特异性。血清 miR-375 也是该疾病预后的新型标志物。目前正在进行进一步的实验以证实我们的结果。
