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

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.

RNF185 antisense RNA 1 (RNF185-AS1) promotes proliferation, migration, and invasion in papillary thyroid carcinoma

“…EMT was a process in which cells lose epithelial features and acquire mesenchymal characteristics [14]. The levels of the N-cad, Vim, and ZEB1 have been reported to be upregulated during EMT in PTC [22–24]. Our western blot and IHC results presented that when RNF185-AS1 was repressed, the levels of N-cad, Vim, and ZEB1 decreased, indicating that RNF185-AS1 indeed took part in EMT in PTC.…”

Artificial Intelligence for Thyroid Nodule Characterization: Where Are We Standing?

“…Several AI and ML approaches were implemented for the classification of thyroid nodules and the early detection of cancers, including modifications to the American College of Radiology Thyroid Imaging Reporting and Data System (TIRADS) systems that may be manually applied. Furthermore, a convolutional neural-network-based CAD program may help in predicting the BRAFV600E genetic mutation [ 54 , 55 , 56 ].…”

Advanced Differentiated Thyroid Cancer: A Complex Condition Needing a Tailored Approach

“…Finally, systemic therapy may be considered in patients with locally advanced and/or metastatic RAI refractory disease not suitable for local therapies with the purpose to reduce tumour growth and/or metastatic spread (43). The first-line systemic therapy is represented by the multikinase inhibitors lenvatinib and sorafenib, approved by FDA and EMA (44)(45)(46)(47)(48)(49). In our series, we have two patients enrolled by endocrinologists for systemic therapy with lenvatinib, as described before: one for local advanced and metastatic disease who refused intervention and the other for multiple recurrent metastatic DTCs (4).…”