MicroRNA‐222 and MicroRNA‐146b are tissue and circulating biomarkers of recurrent papillary thyroid cancer

Abstract

BACKGROUND: Papillary thyroid cancer (PTC) persistence or recurrence and the need for long-term surveillance can cause significant inconvenience and morbidity in patients. Currently, recurrence risk stratification is accomplished by using clinicopathologic factors, and serum thyroglobulin is the only commercially available marker for persistent or recurrent disease. The objective of this study was to determine microRNA (miRNA) expression in PTC and determine whether 1 or more miRNAs could be measured in plasma as a biomarker for recurrence. METHODS: Patients with recurrent PTC (Rc-PTC) and those without recurrence (NR-PTC) were retrospectively recruited for a comparison of their tumor miRNA profiles. Patients with either newly diagnosed PTC or multinodular goiter who were undergoing total thyroidectomy were prospectively recruited for an analysis of preoperative and postoperative circulating miRNA levels. Healthy volunteers were recruited as the control group. RESULTS: MicroRNA-222 and miR-146b were over-expressed 10.8-fold and 8.9-fold, respectively, in Rc-PTC tumors compared with NR-PTC tumors (P 5.014 and P 5.038, respectively). In plasma from preoperative PTC patients, levels of miR-222 and miR-146b were higher compared with the levels in plasma from healthy volunteers (P <.01 for both). Reductions of 2.7-fold and 5.1-fold were observed in the plasma levels of miR-222 and miR-146b, respectively, after total thyroidectomy (P 5.03 for both). CONCLUSIONS: This study demonstrated that tumor levels of miR-222 and miR-146b are associated with PTC recurrence and that miR-222 and miR-146b levels in the circulation correspond to the presence of PTC. The potential of these miRNAs as tumor biomarkers to improve patient stratification according to the risk of recurrence and as circulating biomarkers for PTC surveillance warrants further study. Cancer 2013;119:4358-65.

The combined use of miRNAs and mRNAs as biomarkers for the diagnosis of papillary thyroid carcinoma

“…Recent studies have demonstrated that some miRNAs have the potential to be used as diagnostic or prognostic markers for PTC (24,31). Combining two or three markers constitutes a more accurate approach to differentiating malignant tumors from their benign counterparts when compared with using a single biomarker (32)(33)(34).…”

ENDOCRINE TUMOURS: Advances in the molecular pathogenesis of thyroid cancer: lessons from the cancer genome

“…MiR-146b appears to be a prognostic factor for PTC, as it is associated with aggressive clinicopathological features and a poor clinical outcome (37). It has also been proven to be elevated in the serum of patients with PTC and some of its target genes have been validated in thyroid cancer (38,39). MiR-146b specifically represses PAX8 and NIS, two genes essential for determining the differentiate phenotype of thyroid cancer (40).…”

MicroRNAs as novel biomarkers for the differentiation of malignant versus benign thyroid lesions: a meta-analysis

“…When lesion results are interpreted as indeterminate, thyroidectomy is commonly recommended as a second surgical procedure, because indeterminate may be consistent with malignancy (Faquin and Baloch, 2010;Layfield et al, 2010). However, only 20-30% of the indeterminate lesions have a malignancy risk because up to 80% of indeterminate lesions are benign, making a significant number of surgeries potentially avoidable (Khan et al, 2013;Lee et al, 2013). A combination of other diagnostic procedures have been used to solve the problem, such as the safe, sensitive, and straightforward ultrasonography method; however, this method is only effective with suspicious thyroid nodules, and is ineffective with improving the accuracy of FNAB cytology in indeterminate lesions (Banks et al, 2008;Dean and Gharib, 2008).…”