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.
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.
Authors: Azra Krek; Dominic Grün; Matthew N Poy; Rachel Wolf; Lauren Rosenberg; Eric J Epstein; Philip MacMenamin; Isabelle da Piedade; Kristin C Gunsalus; Markus Stoffel; Nikolaus Rajewsky Journal: Nat Genet Date: 2005-04-03 Impact factor: 38.330
Authors: Joseph Paul Eder; Geoffrey I Shapiro; Leonard J Appleman; Andrew X Zhu; Dale Miles; Harold Keer; Belinda Cancilla; Felix Chu; Suzanne Hitchcock-Bryan; Laurie Sherman; Stewart McCallum; Elisabeth I Heath; Scott A Boerner; Patricia M LoRusso Journal: Clin Cancer Res Date: 2010-05-14 Impact factor: 12.531
Authors: A Belfiore; P Gangemi; A Costantino; G Russo; G M Santonocito; O Ippolito; M F Di Renzo; P Comoglio; A Fiumara; R Vigneri Journal: J Clin Endocrinol Metab Date: 1997-07 Impact factor: 5.958
Authors: Heather C Nardone; Amy F Ziober; Virginia A LiVolsi; Susan J Mandel; Zubair W Baloch; Randal S Weber; Rosemarie Mick; Barry L Ziober Journal: Cancer Date: 2003-10-01 Impact factor: 6.860
Authors: Benjamin P Lewis; I-hung Shih; Matthew W Jones-Rhoades; David P Bartel; Christopher B Burge Journal: Cell Date: 2003-12-26 Impact factor: 41.582
Authors: Patricia Aragon Han; Hyun-seok Kim; Soonweng Cho; Roghayeh Fazeli; Alireza Najafian; Hunain Khawaja; Melissa McAlexander; Benzon Dy; Meredith Sorensen; Anna Aronova; Thomas J Sebo; Thomas J Giordano; Thomas J Fahey; Geoffrey B Thompson; Paul G Gauger; Helina Somervell; Justin A Bishop; James R Eshleman; Eric B Schneider; Kenneth W Witwer; Christopher B Umbricht; Martha A Zeiger Journal: Thyroid Date: 2016-03-07 Impact factor: 6.568