ETA2024 Poster Presentations Translational thyroid cancer research-1 (10 abstracts)
Expression of HSA-MIR-139-5P as a clinically feasible prognostic marker for thyroid cancer
Natalia Martínez-Puente 1,2 , Ignacio Ruz-Caracuel 3,4 , Luis Javier Leandro-García 1 , Héctor Pian-Arias 3 , Zaira Vega-Corral 5 , Rocío Letón 1 , Roberta Radu 1 , Mariolga Berrizbeitia 1 , Sara Mellid 1 , Clara Reglero 1 , Milton Eduardo Salazar-Hidalgo 1 , Ester Arroba 1 , Alberto Díaz-Talavera 1,2 , Mónica Marazuela 6 , Amparo Benito-Berlinches 3 , Irene González-García 3 , Sandra Campos-Mena 7 , María Dolores Lozano-Escario 8 , Sonsoles Guadalix 9 , María Calatayud 10 , Ana Pérez-Campos 11 , Marcos Lahera 6 , Alberto Cascón 1,2 , Juan C. Galofré 12 , Maria Currás-Freixes 13 , Eduardo J. Caleiras 5 , Pablo Valderrabano 7 , Mercedes Robledo 1,2 & Cristina Montero-Conde 1,2
1Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; 2Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Madrid, Spain; 3Department of Pathology, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain; 4Biomedical Research Networking Centre on Cancer (CIBERONC), Institute of Health Carlos III, Madrid, Spain; 5Histopathology Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; 6Endocrinology and Nutrition Department, Hospital Universitario La Princesa, Madrid, Spain; 7Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain; 8Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain; 9Department of Endocrinology, Clínica Universidad de Navarra, Madrid, Spain; 10Endocrinology and Nutrition Department, Hospital Universitario 12 de Octubre, Madrid, Spain; 11Department of Pathology, Hospital Universitario 12 de Octubre, Madrid, Spain. 12Department of Endocrinology, Clínica Universidad de Navarra, Pamplona, Spain; 13Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Introduction: Patients with advanced differentiated thyroid cancer are often radioiodine refractory and present worse outcome with increased mortality1. Early identification is critical for the appropriate disease management and follow-up2. In this regard, we previously found that hsa-miR-139-5p (miR139-5p) down-expression is associated with recurrent/persistent disease3. Furthermore, miR139-5p down-expression has recently been associated with refractoriness to radioiodine therapy4.
Objectives: Here, we evaluate miR139-5p expression in a retrospective long-term follow-up thyroid cancer series enriched with poor prognosis cases to validate the prognostic value of miR139-5p expression and estimate a threshold to dichotomize the cases. In addition, we explore the feasibility of incorporating miR139-testing into the clinical setting using an automated in situ hybridization (ISH) technique.
Methods: DNA and RNA were extracted from formalin-fixed paraffin-embedded tissue sections of normal thyroid tissue, thyroid tumors and metastases (when available) from 60 patients with either progressive/persistent disease (DP/PD) or an excellent response (ER) to primary treatment. The tumor series was analyzed for recurrent tumor driver mutations and TERT promoter (TERT prom) mutations. MiR139-5p expression was measured by qPCR and the geometric mean of 4 housekeeping miRNAs was used as a normalizer. An ISH assay for pre-miR139 detection was optimized by CNIO Histopathology Unit to test miR139 expression in whole tissue sections, using the Discovery ULTRA platform (Roche). Spatial expression of pre-miR139 was quantified and correlated with the prognostic immunohistochemical marker Ki-67 by quantitative image analysis (QuPath v0.5.0).
Results: Paired tumor/normal data analysis confirms a statistically significant miR139-5p expression reduction in tumors, which is more significant in DP/PD-related primary tumors and metastases than in ER-related primary tumors. Furthermore, the distribution of miR139-5p expression in ER- and DP/PD-related primary tumors reveals that extreme expression intervals are disease outcome specific. Notably, 4 of the 8 tumors correctly classified as DP/PD according to miR139-5p expression intervals are negative for TERT prom mutations, a known prognostic marker. Finally, ISH assays support the results observed by qPCR and reveal heterogeneous pre-miR139 expression, which inversely correlates with that of Ki-67.
Conclusion: Our results validate miR139-5p expression analysis as a prognostic marker in thyroid cancer, which may add sensitivity to the prognostic power of TERT prom mutations. In addition, this study underscores the clinical feasibility of incorporating miR139-testing into the clinical practice.
References: 1Haugen, Alexander, Bible et al., Thyroid 2016.
2Gulec, Ahuja, Avram et al., Thyroid 2021.
3Montero-Conde, Graña-Castro, Martín-Serrano et al., Int J Cancer 2020.
4Pecce, Sponziello, Verrienti et al., J Endocrinol Invest 2023
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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