miRNA Expression Pattern in Papillary Thyroid Cancer. miRNA Expression Pattern in Papillary Thyroid Cancer

The aim of this study was to conduct a comparison of tissue miRNA in thyroid cancer (papillary (PTC), follicular (FTC), and microcancer (PTMC)) and healthy thyroid tissue (Control). The expression level of 798 miRNAs using NanoString technology was examined. ROC curve analysis, and logistic regression modeling were performed. Gene ontology (GO), canonical pathways analysis were used to explore the biological functions of the miRNA target genes. The study revealed that 10 miRNAs were deregulated in samples of patients with PTC. Pathway analysis showed that miRNA target genes were mainly significantly enriched in endocrine resistance, EGFR tyrosine kinase inhibitor resistance, and pathways in cancer. ROC analysis demonstrated that miR-146-5p, miR-551b-3p, and miR-222-3p can be introduced as a diagnostic tool for PTC (AUC=0.770; 0.740; 0.720; respectively). Validation by qRT-PCR confirmed our findings. The results suggest that tissue miRNAs can potentially be used as predictive biomarkers of PTC in patients. Overall design: A total of 111 FFFPE samples were included in the study. miRNA profile in 49 PTCs, 7 FTCs, 5 PTMCs and matched 50 normal thyroid samples was analyzed.

本研究旨在对比甲状腺癌（乳头状甲状腺癌（papillary thyroid carcinoma, PTC）、滤泡状甲状腺癌（follicular thyroid carcinoma, FTC）及乳头状甲状腺微癌（papillary thyroid microcarcinoma, PTMC））组织与健康甲状腺组织（对照组，Control）中的组织微小RNA（miRNA）表达差异。本研究采用NanoString技术检测了798种miRNA的表达水平，随后开展了受试者工作特征（Receiver Operating Characteristic, ROC）曲线分析与逻辑回归建模，并通过基因本体（Gene Ontology, GO）分析、经典通路分析对miRNA靶基因的生物学功能进行探究。

研究结果显示，乳头状甲状腺癌患者的样本中共有10种miRNA表达失调。通路分析表明，miRNA靶基因主要显著富集于内分泌抵抗、表皮生长因子受体（Epidermal Growth Factor Receptor, EGFR）酪氨酸激酶抑制剂抵抗以及癌症相关通路中。受试者工作特征曲线分析证实，miR-146-5p、miR-551b-3p及miR-222-3p可作为乳头状甲状腺癌的诊断标志物，其曲线下面积（Area Under Curve, AUC）分别为0.770、0.740及0.720。通过定量实时聚合酶链反应（quantitative real-time PCR, qRT-PCR）验证，本研究的结论得到了证实。

研究结果提示，组织miRNA有望成为乳头状甲状腺癌患者的预测性生物标志物。

实验整体设计：本研究共纳入111份FFFPE样本，对49份乳头状甲状腺癌样本、7份滤泡状甲状腺癌样本、5份乳头状甲状腺微癌样本及匹配的50份正常甲状腺样本的miRNA表达谱进行了分析。