Verrienti Antonella, Pecce Valeria, Grani Giorgio, Del Gatto Valeria, Barp Samuele, Maranghi Marianna, Giacomelli Laura, Di Gioia Cira, Biffoni Marco, Filetti Sebastiano, Durante Cosimo, Sponziello Marialuisa
Department of Translational and Precision Medicine, Sapienza University of Rome, V.le del Policlinico 155, Rome, 00161, Italy.
Department of Surgical Sciences, Sapienza University of Rome, Rome, 00161, Italy.
J Endocrinol Invest. 2025 Mar;48(3):619-631. doi: 10.1007/s40618-024-02467-3. Epub 2024 Sep 19.
Papillary thyroid carcinoma (PTC) is the most common malignant thyroid neoplasm, accounting for approximately 85% of all follicular cell-derived thyroid nodules. This study aimed to assess the diagnostic potential of circulating microRNA-146a-5p and microRNA-221-3p as biomarkers for PTC and their usefulness in monitoring disease progression during patient follow-up.
An observational study was conducted on two cohorts of PTC patients and healthy controls (HCs) using digital PCR. We collected patients' clinical, biochemical, and imaging data during the post-surgery surveillance. We analyzed the levels of circulating miRNAs in serum samples of patients before surgery and during the follow-up, including those with indeterminate/biochemical incomplete response (IndR/BIR) and residual thyroid tissues (Thy Residue).
Both miR-146a-5p and miR-221-3p were confirmed as effective biomarkers for PTC diagnosis. They enabled differentiation between pre-surgery PTC patients and HCs with an area under the curve (AUC) of 92% and 87.3%, respectively, using a threshold level of 768,545 copies/uL for miR-146a-5p and 389,331 copies/uL for miR-221-3p. It was found that miRNA fold change levels, rather than absolute levels, can be useful during patient follow-up. In particular, we found that a fold change of 2 for miR-146a-5p and 2.2 for miR-221-3p can identify a progressive disease, regardless of the presence of TgAbs or remnant thyroid.
MiRNA-146a-5p and miRNA-221-3p, particularly the former, could be valuable diagnostic biomarkers for PTCs. They also seem to be effective in monitoring disease progression during patient follow-up by evaluating their fold change, even when thyroglobulin is uninformative.
甲状腺乳头状癌(PTC)是最常见的甲状腺恶性肿瘤,约占所有滤泡细胞源性甲状腺结节的85%。本研究旨在评估循环微小RNA-146a-5p和微小RNA-221-3p作为PTC生物标志物的诊断潜力及其在患者随访期间监测疾病进展的效用。
使用数字PCR对两组PTC患者和健康对照(HCs)进行了一项观察性研究。我们在术后监测期间收集了患者的临床、生化和影像学数据。我们分析了患者术前和随访期间血清样本中循环miRNA的水平,包括那些具有不确定/生化不完全缓解(IndR/BIR)和残余甲状腺组织(甲状腺残余物)的患者。
miR-146a-5p和miR-221-3p均被确认为PTC诊断的有效生物标志物。使用miR-146a-5p的阈值水平为768,545拷贝/微升和miR-221-3p的阈值水平为389,331拷贝/微升,它们能够区分术前PTC患者和HCs,曲线下面积(AUC)分别为92%和87.3%。研究发现,miRNA倍数变化水平而非绝对水平在患者随访期间可能有用。特别是,我们发现miR-146a-5p的倍数变化为2和miR-221-3p的倍数变化为2.2可以识别疾病进展,无论是否存在TgAbs或残余甲状腺。
微小RNA-146a-5p和微小RNA-221-3p,尤其是前者,可能是PTC的有价值诊断生物标志物。通过评估其倍数变化,它们似乎在患者随访期间监测疾病进展方面也有效,即使甲状腺球蛋白无信息价值时也是如此。