Endocrine Abstracts

Background: Papillary thyroid carcinoma (PTC) is the most frequent subtype of thyroid cancers. Despite good prognosis in most cases, postsurgery recurrences and metastases can occur. Moreover, differential diagnosis between benign and malignant nodules is still challenging. Gaining knowledge about extracellular vesicles (EVs) in PTC could have a double benefit: a better understanding of PTC clinical behaviour, and the discovery of accessible (and accurate) diagnostic tools.

Aims: The goals of this project are to (i) identify miRNAs actors and markers, released via EVs by the tumor, (ii) decipher the mechanisms by which they impact thyroid cancer and its microenvironment, and (iii) evaluate the diagnostic value of circulating miRNAs.

Methods and results: Using a mouse model mimicking human PTC, we isolated EVs from dissociated control- and early and late PTC-tissue by differential ultracentrifugations. Vesicles in the high-speed pellet were characterized in-depth and sequencing was performed to identify tumor-derived EV-miRNAs. We focused on 4 miRNAs differentially more abundant in EVs from PTC tissues. In silico analysis revealed their enrichment in immune-related pathways, consistently with the massive recruitment of macrophages observed in our model. We investigated the distribution of EV-miRNAs according to their cellular source. Using the Nanoview technique, we showed that the number of EVs bearing epithelial and immune markers was increased in PTC tissues. The 4 miRNAs were mostly expressed, and deregulated, in epithelial cells. We thus propose that their increased abundance in epithelial-EVs could affect the immune microenvironment. In parallel, the miRNAs candidates were quantified in tissues, in plasma and in plasma-EVs from patients treated for thyroid diseases. Two miRNAs, miR-146b-5p and miR-21a-5p were more abundant in tissue and plasma-EVs isolated from patients with PTC, as compared to benign diseases.

Conclusions: We provided a gradual tissue- and EV-miRNAs profiling during PTC development which allowed the identification of EV-miRNAs that could (i) support the establishment of a permissive microenvironment for tumor development and (ii) contribute to thyroid cancer diagnosis.