The molecular and gene/miRNA expression profiles of radioiodine resistant papillary thyroid cancer
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RESEARCH
(2020) 39:245
Open Access
The molecular and gene/miRNA expression profiles of radioiodine resistant papillary thyroid cancer Carla Colombo1,2† , Emanuela Minna3† , Chiara Gargiuli4† , Marina Muzza5 , Matteo Dugo4 , Loris De Cecco4 , Gabriele Pogliaghi5 , Delfina Tosi6 , Gaetano Bulfamante6 , Angela Greco3 , Laura Fugazzola1,2* and Maria Grazia Borrello3*
Abstract Background: Papillary thyroid cancer (PTC) is the most frequent endocrine tumor. Radioiodine (RAI) treatment is highly effective in these tumors, but up to 60% of metastatic cases become RAI-refractory. Scanty data are available on either the molecular pattern of radioiodine refractory papillary thyroid cancers (PTC) or the mechanisms responsible for RAI resistance. Methods: We analyzed the molecular profile and gene/miRNA expression in primary PTCs, synchronous and RAIrefractory lymph node metastases (LNMs) in correlation to RAI avidity or refractoriness. We classified patients as RAI+/D+ (RAI uptake/disease persistence), RAI−/D+ (absent RAI uptake/disease persistence), and RAI+/D- (RAI uptake/disease remission), and analyzed the molecular and gene/miRNA profiles, and the expression of thyroid differentiation (TD) related genes. Results: A different molecular profile according to the RAI class was observed: BRAFV600E cases were more frequent in RAI−/D+ (P = 0.032), and fusion genes in RAI+/D+ cases. RAI+/D- patients were less frequently pTERT mutations positive, and more frequently wild type for the tested mutations/fusions. Expression profiles clearly distinguished PTC from normal thyroid. On the other hand, in refractory cases (RAI+/D+ and RAI−/D+) no distinctive PTC expression patterns were associated with either tissue type, or RAI uptake, but with the driving lesion and BRAF−/RAS-like subtype. Primary tumors and RAI-refractory LNMs with BRAFV600E mutation display transcriptome similarity suggesting that RAI minimally affects the expression profiles of RAI-refractory metastases. Molecular profiles associated with the expression of TPO, SLC26A4 and TD genes, that were found more downregulated in BRAFV600E than in gene fusions tumors. (Continued on next page)
* Correspondence: [email protected]; [email protected] † Carla Colombo, Emanuela Minna, Chiara Gargiuli contributed equally as first author. 1 Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy 2 Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy 3 Department of Research, Molecular Mechanisms Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licen
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