Context: Trends toward more conservative management of papillary thyroid cancer (PTC) diminish the primacy of serum thyroglobulin (Tg) assays as a posttreatment surveillance tool. Objective: To identify thyroid tumor-associated microRNAs (miRNAs) in the serum with potential for development as unique biomarkers of PTC recurrence. Methods: We measured expression of 754 miRNAs in serum samples collected from 11 patients with PTC before and 30 days after thyroidectomy. Major candidates were then re-evaluated by absolute quantitative polymerase chain reaction analysis in an independent cohort of patients with PTC (n = 44) or benign nodules and 20 healthy controls (HCs). The 2 miRNAs most significantly associated with thyroid tumors were then assessed in matched serum samples (before and 30 days and 1 to 2 years after surgery) from the 20 PTC patients with complete follow-up datasets and results correlated with American Thyroid Association (ATA) responses to therapy. Results: Eight miRNAs (miR-221-3p, miR-222-3p, miR-146a-5p, miR-24-3p, miR-146b-5p, miR-191-5p, miR-103a-3p, and miR-28-3p) displayed levels in prethyroidectomy serum samples from patients with PTC that significantly exceeded those measured after thyroidectomy and those found in samples from HCs. The 2 most promising candidates—miR-146a-5p and miR-221-3p —were further analyzed in the 20 PTC patients mentioned earlier. Serum levels of both miRNAs after 1 to 2 years of follow-up were consistent with ATA responses to therapy in all patients, including 2 with structural evidence of disease whose Tg assays remained negative (,1 ng/mL). Conclusion: miR-146a-5p and miR-221-3p hold remarkable promise as serum biomarkers for posttreatment monitoring of PTC patients, especially when Tg assay results are uninformative.
Identification of thyroid-associated serum microRNA profiles and their potential use in thyroid cancer follow-up / Rosignolo, Francesca; Sponziello, Marialuisa; Giacomelli, Laura; Diego, Russo; Pecce, Valeria; Biffoni, Marco; Rocco, Bellantone; Celestino Pio, Lombardi; Lamartina, Livia; Grani, Giorgio; Durante, Cosimo; Filetti, Sebastiano; Verrienti, Antonella. - In: JOURNAL OF THE ENDOCRINE SOCIETY. - ISSN 2472-1972. - STAMPA. - 1:1(2017), pp. 3-13. [10.1210/js.2016-1032]
Identification of thyroid-associated serum microRNA profiles and their potential use in thyroid cancer follow-up
ROSIGNOLO, FRANCESCA;SPONZIELLO, Marialuisa;GIACOMELLI, Laura;PECCE, VALERIA;BIFFONI, Marco;LAMARTINA, LIVIA;GRANI, Giorgio;DURANTE, COSIMO;FILETTI, SEBASTIANO;VERRIENTI, Antonella
2017
Abstract
Context: Trends toward more conservative management of papillary thyroid cancer (PTC) diminish the primacy of serum thyroglobulin (Tg) assays as a posttreatment surveillance tool. Objective: To identify thyroid tumor-associated microRNAs (miRNAs) in the serum with potential for development as unique biomarkers of PTC recurrence. Methods: We measured expression of 754 miRNAs in serum samples collected from 11 patients with PTC before and 30 days after thyroidectomy. Major candidates were then re-evaluated by absolute quantitative polymerase chain reaction analysis in an independent cohort of patients with PTC (n = 44) or benign nodules and 20 healthy controls (HCs). The 2 miRNAs most significantly associated with thyroid tumors were then assessed in matched serum samples (before and 30 days and 1 to 2 years after surgery) from the 20 PTC patients with complete follow-up datasets and results correlated with American Thyroid Association (ATA) responses to therapy. Results: Eight miRNAs (miR-221-3p, miR-222-3p, miR-146a-5p, miR-24-3p, miR-146b-5p, miR-191-5p, miR-103a-3p, and miR-28-3p) displayed levels in prethyroidectomy serum samples from patients with PTC that significantly exceeded those measured after thyroidectomy and those found in samples from HCs. The 2 most promising candidates—miR-146a-5p and miR-221-3p —were further analyzed in the 20 PTC patients mentioned earlier. Serum levels of both miRNAs after 1 to 2 years of follow-up were consistent with ATA responses to therapy in all patients, including 2 with structural evidence of disease whose Tg assays remained negative (,1 ng/mL). Conclusion: miR-146a-5p and miR-221-3p hold remarkable promise as serum biomarkers for posttreatment monitoring of PTC patients, especially when Tg assay results are uninformative.File | Dimensione | Formato | |
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