Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, Canada.
International Research Center, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
J Hum Genet. 2019 May;64(5):505-508. doi: 10.1038/s10038-019-0583-7. Epub 2019 Mar 6.
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, wherein diagnostic limitations and lack of accurate prognostic factors are important clinical challenges. In this study, we report the discovery of 234 novel miRNAs in non-neoplastic thyroid and PTC samples, obtained from publicly available small RNA sequencing datasets (TCGA and GEO). These sequences were observed to display similar molecular features compared to currently annotated miRNAs. These potentially novel miRNAs presented tissue-specificity and largely decreased expression in PTC compared to non-neoplastic samples. We showed that the disrupted novel miRNAs have diagnostic and prognostic potential, and were associated with BRAF mutation, a frequent alteration related to more aggressive PTC. In conclusion, our results expand the miRNA repertoire in thyroid tissues and highlight the potential biological role and clinical utility of previously unannotated miRNAs.
甲状腺乳头状癌(PTC)是最常见的甲状腺恶性肿瘤,其诊断局限性和缺乏准确的预后因素是重要的临床挑战。在这项研究中,我们报告了在非肿瘤性甲状腺和 PTC 样本中发现的 234 种新的 miRNA,这些样本来自公开的小 RNA 测序数据集(TCGA 和 GEO)。与目前已注释的 miRNA 相比,这些序列显示出相似的分子特征。这些潜在的新 miRNA 表现出组织特异性,与非肿瘤性样本相比,在 PTC 中表达水平显著降低。我们表明,这些失调的新 miRNA 具有诊断和预后潜力,并与 BRAF 突变相关,BRAF 突变是一种与侵袭性更强的 PTC 相关的常见改变。总之,我们的研究结果扩展了甲状腺组织中的 miRNA 谱,并强调了以前未注释的 miRNA 的潜在生物学作用和临床应用。