Circulating miR-26b-5p and miR-451a as diagnostic biomarkers in medullary thyroid carcinoma patients
Zein Mersini Besharat, Sofia Trocchianesi, Antonella Verrienti, Raffaele Ciampi, Silvia Cantara, Cristina Romei, Claudia Sabato, Teresa Noviello, Agnese Pò, Anna Citarella, Francesca Pia Caruso, Ilaria Panariello, Francesca Gianno, Guido Carpino, Eugenio Gaudio, Martina Chiacchiarini, Laura Masuelli, Marialuisa Sponziello, Valeria Pecce, Teresa Ramone, Fabio Maino, Francesco Dotta, Michele Ceccarelli, Luciano Pezzullo, Cosimo Durante, Maria Grazia Castagna, Rossella Elisei, Elisabetta Ferretti
Abstract
PURPOSE/METHODS: The determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis is still challenging. The aim of this study was to identify non-invasive circulating biomarkers in MTC. To achieve this goal, paired MTC tissue and plasma extracellular vesicle samples were collected from multiple centres and microRNA (miRNA) expression levels were evaluated. RESULTS: The samples from a discovery cohort of 23 MTC patients were analysed using miRNA arrays. Lasso logistic regression analysis resulted in the identification of a set of circulating miRNAs as diagnostic biomarkers. Among them, miR-26b-5p and miR-451a, were highly expressed and their expression decreased during follow-up in disease-free patients in the discovery cohort. Circulating miR-26b-5p and miR-451a were validated using droplet digital PCR in a second independent cohort of 12 MTC patients. CONCLUSION: This study allowed the identification and validation of a signature of two circulating miRNAs, miR-26b-5p and miR-451a, in two independent cohorts reporting a significant diagnostic performance for MTC. The results of this study offer advancements in molecular diagnosis of MTC proposing a novel non-invasive tool to use in precision medicine.