Rosignolo Francesca, Sponziello Marialuisa, Giacomelli Laura, Russo Diego, Pecce Valeria, Biffoni Marco, Bellantone Rocco, Lombardi Celestino Pio, Lamartina Livia, Grani Giorgio, Durante Cosimo, Filetti Sebastiano, Verrienti Antonella
Dipartimento di Medicina Interna e Specialità Mediche and.
Dipartimento di Scienze Chirurgiche, Università di Roma "Sapienza", Viale del Policlinico 155, 00161 Rome, Italy.
J Endocr Soc. 2017 Jan 12;1(1):3-13. doi: 10.1210/js.2016-1032. eCollection 2017 Jan 1.
Trends toward more conservative management of papillary thyroid cancer (PTC) diminish the primacy of serum thyroglobulin (Tg) assays as a posttreatment surveillance tool.
To identify thyroid tumor-associated microRNAs (miRNAs) in the serum with potential for development as unique biomarkers of PTC recurrence.
We measured expression of 754 miRNAs in serum samples collected from 11 patients with PTC before and 30 days after thyroidectomy. Major candidates were then re-evaluated by absolute quantitative polymerase chain reaction analysis in an independent cohort of patients with PTC (n = 44) or benign nodules and 20 healthy controls (HCs). The 2 miRNAs most significantly associated with thyroid tumors were then assessed in matched serum samples (before and 30 days and 1 to 2 years after surgery) from the 20 PTC patients with complete follow-up datasets and results correlated with American Thyroid Association (ATA) responses to therapy.
Eight miRNAs (miR-221-3p, miR-222-3p, miR-146a-5p, miR-24-3p, miR-146b-5p, miR-191-5p, miR-103a-3p, and miR-28-3p) displayed levels in prethyroidectomy serum samples from patients with PTC that significantly exceeded those measured after thyroidectomy and those found in samples from HCs. The 2 most promising candidates-miR-146a-5p and miR-221-3p -were further analyzed in the 20 PTC patients mentioned earlier. Serum levels of both miRNAs after 1 to 2 years of follow-up were consistent with ATA responses to therapy in all patients, including 2 with structural evidence of disease whose Tg assays remained negative (<1 ng/mL).
miR-146a-5p and miR-221-3p hold remarkable promise as serum biomarkers for post-treatment monitoring of PTC patients, especially when Tg assay results are uninformative.
甲状腺乳头状癌（PTC）管理趋于保守的趋势降低了血清甲状腺球蛋白（Tg）检测作为治疗后监测工具的首要地位。
鉴定血清中与甲状腺肿瘤相关的微小RNA（miRNA），其有潜力发展成为PTC复发的独特生物标志物。
我们检测了11例PTC患者甲状腺切除术前及术后30天采集的血清样本中754种miRNA的表达。然后在另一组独立的PTC患者（n = 44）、良性结节患者及20名健康对照（HC）中，通过绝对定量聚合酶链反应分析对主要候选miRNA进行重新评估。随后在20例有完整随访数据集的PTC患者的配对血清样本（术前、术后30天及术后1至2年）中评估与甲状腺肿瘤最显著相关的2种miRNA，并将结果与美国甲状腺协会（ATA）的治疗反应相关联。
8种miRNA（miR-221-3p、miR-222-3p、miR-146a-5p、miR-24-3p、miR-146b-5p、miR-191-5p、miR-103a-3p和miR-28-3p）在PTC患者甲状腺切除术前血清样本中的水平显著高于甲状腺切除术后及HC样本中的水平。在上述20例PTC患者中对最有前景的2种候选miRNA——miR-146a-5p和miR-221-3p进行了进一步分析。在所有患者中，随访1至2年后这两种miRNA的血清水平均与ATA的治疗反应一致，包括2例Tg检测仍为阴性（<1 ng/mL）但有疾病结构证据的患者。
miR-146a-5p和miR-221-3p作为PTC患者治疗后监测的血清生物标志物具有显著前景，尤其是在Tg检测结果无信息价值时。
