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Circulating miR-375 as a novel prognostic marker for metastatic medullary thyroid cancer patients.

Circulating miR-375 as a novel prognostic marker for metastatic medullary thyroid cancer patients.
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Romeo P, Colombo C, Granata R, Calareso G, Gualeni AV, Dugo M, De Cecco L, Rizzetti MG, Zanframundo A, Aiello A, Carcangiu ML, Gloghini A, Ferrero S, Licitra L, Greco A, Fugazzola L, Locati LD, Borrello MG,


Romeo P, Colombo C, Granata R, Calareso G, Gualeni AV, Dugo M, De Cecco L, Rizzetti MG, Zanframundo A, Aiello A, Carcangiu ML, Gloghini A, Ferrero S, Licitra L, Greco A, Fugazzola L, Locati LD, Borrello MG, (click to view)

Romeo P, Colombo C, Granata R, Calareso G, Gualeni AV, Dugo M, De Cecco L, Rizzetti MG, Zanframundo A, Aiello A, Carcangiu ML, Gloghini A, Ferrero S, Licitra L, Greco A, Fugazzola L, Locati LD, Borrello MG,

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Endocrine-related cancer 2018 01 03() pii 10.1530/ERC-17-0389

Abstract

This study aimed to identify circulating miRNAs as novel non-invasive biomarkers for prognosis and vandetanib response in advanced medullary thyroid cancer (MTC) patients. We prospectively recruited two independent cohorts of locally advanced/metastatic MTC patients including a subgroup of vandetanib-treated subjects: a discovery cohort (n = 20), including matched plasma/tissue samples (n = 17/20), and a validation cohort, yielding only plasma samples (n = 17). Plasma samples from healthy subjects (n = 36) and MTC patients in remission (n = 9) were used as controls. MTC (n = 8) and non-neoplastic thyroid specimens (n = 3) were assessed by microarray profiling to identify candidate circulating miRNAs. qRT-PCR and in situ hybridisation were carried out to validate the expression and localization of a selected miRNA within tissues, and qRT-PCR was performed also to measure miRNA levels in plasma samples. We identified 51 miRNAs differentially expressed in MTC. The most over-expressed miR, miR-375, was highly expressed by C cells compared to other thyroid cells, and more expressed in MTC than in reactive C-cell hyperplasia. MTC patients had significantly higher miR-375 plasma levels than healthy controls (P < 0.0001) and subjects in remission (P = 0.0004). MiR-375 plasma levels were not predictive of vandetanib response, but, notably, high levels were associated with significantly reduced overall survival (HR 10.61, P < 0.0001) and were a strong prognostic factor of poor prognosis (HR 6.24, P = 0.00025) in MTC patients. Overall our results unveil plasma miR-375 as a promising prognostic marker for advanced MTC patients, to be validated in larger cohorts.

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