Expression and Clinical Utility of Transcription Factors Involved in Epithelial-Mesenchymal Transition during Thyroid Cancer Progression

甲状腺癌进展过程中参与上皮-间质转化的转录因子的表达和临床应用

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作者:Enke Baldini, Chiara Tuccilli, Daniele Pironi, Antonio Catania, Francesco Tartaglia, Filippo Maria Di Matteo, Piergaspare Palumbo, Stefano Arcieri, Domenico Mascagni, Giorgio Palazzini, Domenico Tripodi, Alessandro Maturo, Massimo Vergine, Danilo Tarroni, Eleonora Lori, Iulia Catalina Ferent, Corrad

Abstract

The transcription factors involved in epithelial-mesenchymal transition (EMT-TFs) silence the genes expressed in epithelial cells (e.g., E-cadherin) while inducing those typical of mesenchymal cells (e.g., vimentin). The core set of EMT-TFs comprises Zeb1, Zeb2, Snail1, Snail2, and Twist1. To date, information concerning their expression profile and clinical utility during thyroid cancer (TC) progression is still incomplete. We evaluated the EMT-TF, E-cadherin, and vimentin mRNA levels in 95 papillary TC (PTC) and 12 anaplastic TC (ATC) tissues and correlated them with patients' clinicopathological parameters. Afterwards, we corroborated our findings by analyzing the data provided by a case study of the TGCA network. Compared with normal tissues, the expression of E-cadherin was found reduced in PTC and more strongly in ATC, while the vimentin expression did not vary. Among the EMT-TFs analyzed, Twist1 seems to exert a prominent role in EMT, being significantly associated with a number of PTC high-risk clinicopathological features and upregulated in ATC. Nonetheless, in the multivariate analysis, none of the EMT-TFs displayed a prognostic value. These data suggest that TC progression is characterized by an incomplete EMT and that Twist1 may represent a valuable therapeutic target warranting further investigation for the treatment of more aggressive thyroid cancers.

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