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

Cancer. 2013 Dec 15;119(24):4358-65. doi: 10.1002/cncr.28254. Epub 2013 Oct 28.


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 = .014 and P = .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 = .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.

Keywords: circulating biomarkers; microRNA; papillary thyroid cancer; recurrence; tissue biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma / blood
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Carcinoma, Papillary
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Prospective Studies
  • Retrospective Studies
  • Thyroglobulin / blood
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / blood
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Thyroidectomy / methods


  • Biomarkers, Tumor
  • MIRN146 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs
  • Thyroglobulin