caa a22 4500 445334029 CHVBK 20180317142747.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1245/s10434-011-1733-0 doi (NATIONALLICENCE)springer-10.1245/s10434-011-1733-0 MicroRNA Signature Distinguishes the Degree of Aggressiveness of Papillary Thyroid Carcinoma [Elektronische Daten] [Linwah Yip, Lindsey Kelly, Yongli Shuai, Michaele Armstrong, Yuri Nikiforov, Sally Carty, Marina Nikiforova] Background: Papillary thyroid carcinoma (PTC) has relatively indolent behavior, although some tumors recur and disseminate to distant sites. The aggressive biological behavior of PTC is difficult to predict. MicroRNAs (miRNAs) are dysregulated in various tumors types, and some of them serve as markers of poor prognosis. In this study, we evaluated miRNA expression as a marker of more aggressive behavior in PTC. Methods: miRNA array was used to identify a subset of differentially expressed miRNAs between aggressive and nonaggressive PTC. These miRNAs were further validated by real-time RT-PCR in a cohort of 17 PTC with local tumor recurrence or distant metastases and 15 PTC with no extrathyroidal dissemination and correlated with BRAF, RAS, and RET/PTC mutations and MET expression. Results: The miRNA array identified miR-146b, miR-221, miR-222, miR-155, miR-31 upregulation and miR-1, miR-34b, miR-130b, miR-138 downregulation in aggressive compared with nonaggressive PTC. Significant miRNA deregulation was confirmed in the validation cohort, with upregulation of miR-146b and miR-222 and downregulation of miR-34b and miR-130b seen in aggressive PTC. Among BRAF-positive tumors, miR-146b showed strong association with aggressive PTC. MET was identified as a potential target gene for 2 downregulated miRNAs (miR-34b and miR-1), and significantly higher level of MET expression was observed in aggressive PTC. Conclusions: We demonstrate that miR-146b, miR-222, miR-34b, miR-130b are differentially expressed in aggressive compared with nonaggressive PTC. Among BRAF-positive tumors, overexpression of miR-146b was associated with aggressive behavior, suggesting that it may further refine the prognostic importance of BRAF. Society of Surgical Oncology, 2011 Yip Linwah Department of Surgery, Section of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut Kelly Lindsey Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut Shuai Yongli University of Pittsburgh Cancer Institute Biostatistics Facility, Pittsburgh, PA, USA aut Armstrong Michaele Department of Surgery, Section of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut Nikiforov Yuri Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut Carty Sally Department of Surgery, Section of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut Nikiforova Marina Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut Annals of Surgical Oncology Springer-Verlag 18/7(2011-07-01), 2035-2041 1068-9265 18:7<2035 2011 18 10434 https://doi.org/10.1245/s10434-011-1733-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-011-1733-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yip Linwah Department of Surgery, Section of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Kelly Lindsey Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Shuai Yongli University of Pittsburgh Cancer Institute Biostatistics Facility, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Armstrong Michaele Department of Surgery, Section of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Nikiforov Yuri Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Carty Sally Department of Surgery, Section of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Nikiforova Marina Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/7(2011-07-01), 2035-2041 1068-9265 18:7<2035 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer