ECEESPE2025 Poster Presentations Thyroid (141 abstracts)
miRNA expression profiles in medullary thyroid carcinoma with HRAS Q61R variant
Karolina Mastnikova 1 , Vlasta Kuklikova 1 , Barbora Bulanova 1 , Olivia Cillikova 1 , Katerina Vyhnalova 1 , Marie Rodová 1 , Eliska Vaclavikova 1 , Jitka Carkova 1 , Rami Katra 2 , Petr Vlcek 3 , Daniela Kodetova 4 , Martin Chovanec 5 , Jana Drozenova 6 , Radoslav Matej 6 , Jaromir Astl 7 , Jiri Hlozek 7 , Jiri Soukup 8 , Josef Vcelak 1 & Bela Bendlova 1
1Institute of Endocrinology, Department of Molecular Endocrinology, Prague, Czech Republic; 22nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Department of Ear, Nose, and Throat, Prague, Czech Republic; 32nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Department of Nuclear Medicine and Endocrinology, Prague, Czech Republic; 42nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Department of Pathology and Molecular Medicine, Prague, Czech Republic; 53rd Faculty of Medicine, Charles University in Prague and University Hospital Kralovske Vinohrady, Department of Otorhinolaryngology, Prague, Czech Republic; 63rd Faculty of Medicine, Charles University in Prague and University Hospital Kralovske Vinohrady, Department of Pathology, Prague, Czech Republic; 73rd Faculty of Medicine and Military University Hospital, Departments of Otorhinolaryngology and Maxillofacial Surgery, Prague, Czech Republic; 83rd Faculty of Medicine and Military University Hospital, Departments of Pathology, Prague, Czech Republic
JOINT3555
Objective: The Q61R variant is the most frequent genetic alteration in the HRAS gene. It is observed in benign nodules, low-risk neoplasms and even malignant tumors including medullary thyroid carcinoma (MTC). Pathogenic variants in the HRAS gene are the ones most frequently detected in RET-negative MTC, but their prognostic significance is still unclear due to their occurrence across both benign and malignant thyroid tissue. Also, the presence of the Q61R variant alone makes it difficult to distinguish MTC from thyroid tumors derived from follicular cells in fine needle aspiration biopsy (FNAB) samples.
Methods: This study investigated miRNA expression profiles in 12 MTC, 12 papillary thyroid carcinoma (PTC) and 6 benign nodules with HRAS Q61R variant. The miRNA libraries for NGS sequencing were prepared from RNA isolated from fresh-frozen thyroid tissues using the QIAseq miRNA Library Kit (Qiagen). To compare miRNA expression of HRAS-positive MTC with HRAS-positive benign tissues and HRAS-positive PTC the miRge3.0 tool and DESeq2 package in R were used.
Results: In HRAS-positive MTC, a significant change in expression was found for 238 miRNAs compared to HRAS positive benign thyroid nodules and for 232 miRNAs compared to HRAS-positive PTC. Some miRNAs with significant expression changes in MTC were the same compared to HRAS-positive benign thyroid nodules and HRAS-positive PTCs (e.g., increased expression of hsa-miR-224-5p, hsa miR-132-3p, hsa-miR-132-5p, hsa-miR-769-5p, hsa-miR 10a 3p and decreased expression of hsa-miR-181a-2-3p and hsa-miR-126-5p), others were unique and were only changed compared to HRAS-positive benign thyroid nodules (e.g., increased expression of hsa-miR-137-3p, hsa-miR-10a 5p and decreased expression of hsa-miR-190a-5p, hsa-miR-130b-5p) or HRAS-positive PTCs (e.g., increased expression of hsa-miR-212-3p, hsa-miR-330-3p and decreased expression of hsa miR 130a-3p, hsa-miR-551b-3p, hsa-miR-30a-5p).
Conclusion: These data indicate the presence of distinct epigenetic alterations, manifesting in the form of altered miRNA expression profiles that may distinguish MTC from thyroid nodules derived from follicular cells in FNAB with the HRAS Q61R variant. Subsequent to the present study, verification will be undertaken using an alternative method, and an analysis of a larger set of samples will be conducted. Supported by AZV NU21-01-00448 and MH CZ RVO 00023761.
Volume 110
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Endocrine Abstracts
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