Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma

Little is known about the function of microRNA-224 (miR-224) in medullary thyroid cancer (MTC). This study investigated the role of miR-224 expression in MTC and correlated it with mutation status in sporadic MTCs. A consecutive series of 134 MTCs were considered. Patients had a sporadic form in 80%...

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Published in:International Journal of Endocrinology 2017-01, Vol.2017 (2017), p.1-9
Main Authors: Vianello, Federica, Zovato, Stefania, Nacamulli, Davide, Mian, Caterina, Iacobone, Maurizio, Censi, Simona, Watutantrige-Fernando, Sara, Galuppini, Francesca, Pennelli, Gianmaria, Bertazza, Loris, Barollo, Susi, Cavedon, Elisabetta, Benna, Clara
Format: Article
Language:English
Subjects:
Clinical outcomes
Endocrinology
Females
Gene expression
Gene mutations
Genetic aspects
Kinases
Medical prognosis
Medical research
MicroRNA
MicroRNAs
Mutation
Patients
Polymerase chain reaction
Software
Studies
Thyroid cancer
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Summary:Little is known about the function of microRNA-224 (miR-224) in medullary thyroid cancer (MTC). This study investigated the role of miR-224 expression in MTC and correlated it with mutation status in sporadic MTCs. A consecutive series of 134 MTCs were considered. Patients had a sporadic form in 80% of cases (107/134). In this group, REarranged during transfection (RET) and rat sarcoma (RAS) mutation status were assessed by direct sequencing in the tumor tissues. Quantitative real-time polymerase chain reaction was used to quantify mature hsa-miR-224 in tumor tissue. RAS (10/107 cases, 9%) and RET (39/107 cases, 36%) mutations were mutually exclusive in sporadic cases. miR-224 expression was significantly downregulated in patients with the following: high calcitonin levels at diagnosis (p=0.03, r=−0.3); advanced stage (p=0.001); persistent disease (p=0.001); progressive disease (p=0.002); and disease-related death (p=0.0001). We found a significant positive correlation between miR-224 expression and somatic RAS mutations (p=0.007). Patients whose MTCs had a low miR-224 expression tended to have a shorter overall survival (log-rank test p=0.005). On multivariate analysis, miR-224 represented an independent prognostic marker. Our data indicate that miR-224 is upregulated in RAS-mutated MTCs and in patients with a better prognosis and could represent an independent prognostic marker in MTC patients.
ISSN:1687-8337
1687-8345
DOI:10.1155/2017/4915736