Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). In a subgroup of patients with PTC, the disease progresses to an invasive stage or in some cases to distant organ metastasis. At present, there is an unmet clinical and diagnostic need for early identification of patients with PTC who are at risk of disease progression or metastasis. In this study, we report several molecular leads and potential biomarker candidates of PTC metastasis for further translational research. The study design was based on comparisons of PTC in three different groups using cross-sectional sampling: Group 1, PTC localized to the thyroid (n = 20); Group 2, PTC with extrathyroidal progression (n = 22); and Group 3, PTC with distant organ metastasis (n = 20). Global transcriptome and microRNAs (miRNA) analyses were conducted using an initial screening set comprising nine formalin-fixed paraffin-embedded PTC samples obtained from three independent patients per study group. The findings were subsequently validated by quantitative real-time polymerase chain reaction (qRT-PCR) using the abovementioned independent patient sample set (n = 62). Comparative analyses of differentially expressed miRNAs showed that miR-193-3p, miR-182-5p, and miR-3607-3p were novel miRNAs associated with PTC metastasis. These potential miRNA biomarkers were associated with TC metastasis and miRNA-target gene associations, which may provide important clinicopathological information on metastasis. Our findings provide new molecular leads for further translational biomarker research, which could facilitate the identification of patients at risk of PTC disease progression or metastasis.

中文翻译：

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使用全局转录组和microRNA分析法绘制乳头状甲状腺癌进展和转移的分子基础和标记。

甲状腺乳头状癌（PTC）是最常见的甲状腺癌（TC）。在患有PTC的患者亚组中，疾病发展为侵入性阶段，在某些情况下甚至发展为远处器官转移。当前，对于早期识别处于疾病发展或转移风险中的PTC患者，存在尚未满足的临床和诊断需求。在这项研究中，我们报告了P​​TC转移的一些分子先导和潜在的生物标志物候选物，用于进一步的翻译研究。该研究设计基于使用横截面采样对三个不同组中PTC的比较：第1组，PTC定位于甲状腺（n = 20）；第2组，甲状腺外进展性PTC（n = 22）；第3组，PTC伴有远处器官转移（n = 20）。使用初始筛选集进行全局转录组和microRNA（miRNA）分析，该初始筛选集包含从每个研究组的三名独立患者获得的九种福尔马林固定石蜡包埋的PTC样品。随后，使用上述独立患者样本集（n = 62）通过实时定量聚合酶链反应（qRT-PCR）验证了发现。差异表达的miRNA的比较分析表明，miR-193-3p，miR-182-5p和miR-3607-3p是与PTC转移相关的新型miRNA。这些潜在的miRNA生物标志物与TC转移和miRNA-靶基因关联相关，这可能提供有关转移的重要临床病理信息。我们的发现为进一步的翻译生物标志物研究提供了新的分子线索，