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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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2017/4915736 |
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| author | Elisabetta Cavedon Susi Barollo Loris Bertazza Gianmaria Pennelli Francesca Galuppini Sara Watutantrige-Fernando Simona Censi Maurizio Iacobone Clara Benna Federica Vianello Stefania Zovato Davide Nacamulli Caterina Mian |
| author_facet | Elisabetta Cavedon Susi Barollo Loris Bertazza Gianmaria Pennelli Francesca Galuppini Sara Watutantrige-Fernando Simona Censi Maurizio Iacobone Clara Benna Federica Vianello Stefania Zovato Davide Nacamulli Caterina Mian |
| author_sort | Elisabetta Cavedon |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-aa834b909f1d4afbb65822439cdcb4e8 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-aa834b909f1d4afbb65822439cdcb4e82025-02-03T01:00:50ZengWileyInternational Journal of Endocrinology1687-83371687-83452017-01-01201710.1155/2017/49157364915736Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid CarcinomaElisabetta Cavedon0Susi Barollo1Loris Bertazza2Gianmaria Pennelli3Francesca Galuppini4Sara Watutantrige-Fernando5Simona Censi6Maurizio Iacobone7Clara Benna8Federica Vianello9Stefania Zovato10Davide Nacamulli11Caterina Mian12Familial Tumor Unit, Veneto Institute of Oncology, (IOV)-IRCCS, Padova, ItalyEndocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, ItalyEndocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, ItalySurgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua, ItalySurgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua, ItalyEndocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, ItalyEndocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, ItalySurgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, ItalySurgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, ItalyDepartment of Radiotherapy, Veneto Institute of Oncology (IOV)-IRCCS, Padova, ItalyFamilial Tumor Unit, Veneto Institute of Oncology, (IOV)-IRCCS, Padova, ItalyEndocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, ItalyEndocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, ItalyLittle 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.http://dx.doi.org/10.1155/2017/4915736 |
| spellingShingle | Elisabetta Cavedon Susi Barollo Loris Bertazza Gianmaria Pennelli Francesca Galuppini Sara Watutantrige-Fernando Simona Censi Maurizio Iacobone Clara Benna Federica Vianello Stefania Zovato Davide Nacamulli Caterina Mian Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma International Journal of Endocrinology |
| title | Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma |
| title_full | Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma |
| title_fullStr | Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma |
| title_full_unstemmed | Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma |
| title_short | Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma |
| title_sort | prognostic impact of mir 224 and ras mutations in medullary thyroid carcinoma |
| url | http://dx.doi.org/10.1155/2017/4915736 |
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