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

Paola Romeo, Carla Colombo, Roberta Granata, Giuseppina Calareso, Ambra Vittoria Gualeni, Matteo Dugo, Loris De Cecco, Maria Grazia Rizzetti, Angela Zanframundo, Antonella Aiello, Maria Luisa Carcangiu, Annunziata Gloghini, Stefano Ferrero, Lisa Licitra, Angela Greco, Laura Fugazzola, Laura Deborah Locati, Maria Grazia Borrello

Research output: Contribution to journalArticlepeer-review


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 = 17 from 8 patients included in discovery cohort) and non-neoplastic thyroid specimens (n = 3) were assessed by microarray profiling to identify candidate circulating miRNAs. qRT-PCR and in situ hybridization were carried out to validate the expression and localization of a selected miRNA within tissues, and qRT-PCR was also performed to measure miRNA levels in plasma samples. By microarray analysis, we identified 51 miRNAs differentially expressed in MTC. The most overexpressed 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) as demonstrated by qRT-PCR analysis. 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.

Original languageEnglish
Pages (from-to)217-231
Number of pages15
JournalEndocrine-Related Cancer
Issue number3
Publication statusPublished - Mar 1 2018


  • Circulating miRNA
  • Medullary thyroid cancer
  • Metastases
  • miR-375
  • Prognostic biomarker

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research


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