title: MicroRNA Expression and Association with Clinicopathologic Features in Papillary Thyroid Cancer: A Systematic Review.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Endocrine Surgery Section, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Aragon Han
authors.affiliation: 1 Endocrine Surgery Section, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Chien-Hsiang
authors.initials: CH
authors.lastname: Weng
authors.affiliation: 1 Endocrine Surgery Section, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Hunain T
authors.initials: HT
authors.lastname: Khawaja
authors.affiliation: 2 Johns Hopkins Surgery Center for Outcomes Research, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Neeraja
authors.initials: N
authors.lastname: Nagarajan
authors.affiliation: 2 Johns Hopkins Surgery Center for Outcomes Research, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Schneider
authors.affiliation: 1 Endocrine Surgery Section, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Umbricht
authors.affiliation: 3 Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Witwer
authors.affiliation: 1 Endocrine Surgery Section, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Martha A
authors.initials: MA
authors.lastname: Zeiger
mesh_terms: D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf