MicroRNA Expression and Association with Clinicopathologic Features in Papillary Thyroid Cancer: A Systematic Review

Thyroid. 2015 Dec;25(12):1322-9. doi: 10.1089/thy.2015.0193. Epub 2015 Oct 8.


Background: Studies have suggested that microRNAs (miR) may be useful prognostic markers and are associated with aggressive clinicopathologic features in papillary thyroid cancer (PTC). This systematic review examined associations between miRs and aggressive clinicopathologic features in PTC.

Methods: A literature search was performed within the PubMed, Embase, Cochrane, Web of Science, and Scopus databases for papers published prior to November 24, 2014. The search was performed by combining the concepts "thyroid tumor" with "microRNA" and by using "and" as the Boolean operator. Upon retrieval of candidate studies, full-text publications were reviewed in their entirety and selected if they examined the prognostic significance between miR expression and established aggressive clinicopathologic features of PTC.

Results: Fifteen studies from 13 unique groups that included 807 patients were reviewed. Most of the studies were retrospective, and none included patients who had undergone routine central lymph node dissection. Expression levels of miRs-21, -34b, -130b, -135b, -146b, -151, -181b, -199b-5p, -221, -222, -451, -623, -1271, -2861, and let-7e showed significant association with at least one aggressive feature, such as large tumor size, extrathyroidal extension, multifocality, lymphovascular invasion, lymph node metastases, distant metastasis, advanced American Joint Cancer Committee stage, and presence of the BRAF(V600E) mutation. Herein we summarize the literature with regard to these associations.

Conclusion: Further studies are needed to investigate whether miRs are independent predictors of aggressive clinicopathologic features before it can be recommended that miR expression levels should be incorporated into the management algorithm for patients with PTC. A well-designed prospective study is needed to assess these potential associations.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma, Papillary
  • Humans
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mutation
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / metabolism
  • Neoplasms, Multiple Primary / pathology
  • Proto-Oncogene Proteins B-raf / genetics
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology
  • Tumor Burden


  • Biomarkers, Tumor
  • MicroRNAs
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf