Zhang Yanqing, Xu Desheng, Pan Jiaqi, Yang Zhengkai, Chen Meijun, Han Jun, Zhang Sijia, Sun Lulu, Qiao Hong
Department of Hematology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150040, P.R. China.
Oncol Lett. 2017 Jun;13(6):4252-4266. doi: 10.3892/ol.2017.6028. Epub 2017 Apr 11.
Circulating microRNAs (miRNAs/miRs) are considered to be potential biomarkers for numerous types of cancer. However, previous investigations into the expression of miRNAs in the serum of patients with papillary thyroid carcinoma (PTC) to predict diagnosis, prognosis and recurrence have reported conflicting results, and the role of miRNAs remains unclear. The present study dynamically assessed the circulating miRNA profile in patients with PTC and determined whether miRNAs in the serum could be used as biomarkers for the diagnosis, prognosis and recurrence of PTC. The expression levels of 3 reportedly upregulated miRNAs (miR-222, miR-221 and miR-146b) were analyzed using reverse transcription-quantitative polymerase chain reaction in 106 patients with PTC, 35 patients with benign thyroid nodules (BTN) and 40 paired controls. Patients with either newly diagnosed PTC or BTN who were undergoing thyroidectomies were recruited for a dynamic analysis of preoperative and postoperative serum miRNA levels. The results indicated that the expression levels of serum miR-222, miR-221 and miR-146b were significantly increased in patients with newly diagnosed PTC compared with controls and patients with BTN. Receiver operating characteristic curve analysis indicated that these miRNAs had a high diagnostic sensitivity and specificity for PTC prior to surgery. The expression of these three miRNAs in serum was significantly associated with poorer prognostic variables, including extrathyroidal invasion, metastatic lymph nodes and high-risk or advanced tumor node metastasis stage. More notably, the present study identified 2.36-, 2.69- and 5.39-fold reductions in the serum levels of miR-222, miR-221 and miR-146b, respectively, subsequent to patients undergoing a thyroidectomy. In addition, miR-222, miR-221 and miR-146b were overexpressed in the PTC with recurrence group compared with the PTC without recurrence group. Collectively, dynamic monitoring of circulating miRNAs may serve as a non-invasive biomarker for the diagnosis of PTC and the postoperative monitoring of its progression and recurrence.
循环微RNA（miRNA/miR）被认为是多种癌症的潜在生物标志物。然而，先前关于甲状腺乳头状癌（PTC）患者血清中miRNA表达以预测诊断、预后和复发的研究报告结果相互矛盾，miRNA的作用仍不明确。本研究动态评估了PTC患者的循环miRNA谱，并确定血清中的miRNA是否可作为PTC诊断、预后和复发的生物标志物。使用逆转录-定量聚合酶链反应分析了106例PTC患者、35例良性甲状腺结节（BTN）患者和40例配对对照中3种据报道上调的miRNA（miR-222、miR-221和miR-146b）的表达水平。招募正在接受甲状腺切除术的新诊断PTC或BTN患者，对术前和术后血清miRNA水平进行动态分析。结果表明，新诊断PTC患者血清miR-222、miR-22l和miR-146b的表达水平与对照和BTN患者相比显著升高。受试者工作特征曲线分析表明，这些miRNA在手术前对PTC具有较高的诊断敏感性和特异性。这三种miRNA在血清中的表达与较差的预后变量显著相关，包括甲状腺外侵犯、转移淋巴结以及高风险或晚期肿瘤淋巴结转移分期。更值得注意的是，本研究发现患者接受甲状腺切除术后，血清中miR-222、miR-221和miR-146b水平分别降低了2.36倍、2.69倍和5.39倍。此外，与无复发的PTC组相比，复发的PTC组中miR-222、miR-221和miR-146b过表达。总体而言，循环miRNA的动态监测可作为PTC诊断及其术后进展和复发监测的非侵入性生物标志物。
