title: Expressions of miRNAs in papillary thyroid carcinoma and their associations with the BRAFV600E mutation.
abstract: OBJECTIVE
  Alterations in microRNA (miRNA) expression have been described in thyroid tumors, suggesting a role for miRNAs in thyroid carcinogenesis. BRAF(V600E) is the most frequently identified genetic alteration in papillary thyroid carcinoma (PTC). We investigated the link between BRAF(V600E) status and the expression of miRNAs in PTC and analyzed the associations of these factors with clinicopathological characteristics.
  
  
  METHODS
  Prospective study of patients who underwent thyroid surgery between October 8, 2008 and November 1, 2010. BRAF(V600E) status was determined by mutant allele-specific amplification PCR and direct sequencing of exon 15 of the BRAF gene in 69 PTC tissues and 69 respective paracancerous normal thyroid tissues. Initially, miRNA expression was analyzed in 12 PTC tissues and three associated paracancerous tissues using a miRNA microarray. miRNAs differentially expressed between BRAF(V600E)-positive and -negative PTC tissues were then validated by real-time quantitative PCR on 69 PTC tissues and 69 paracancerous tissues. We also explored the associations between BRAF(V600E) status or differential miRNA expression and clinicopathological characteristics.
  
  
  RESULTS
  The mutation rate of BRAF(V600E) in PTC was 47.8%. Twelve miRNAs were upregulated and six were downregulated in PTC tissues, among which miR-15a, 15a*, 34a*, 34b*, 551b, 873, 876-3p, and 1274a were first identified. miR-21* and 203 were significantly dysregulated (P<0.05) in PTC tissues with BRAF(V600E). Additionally, there were significant associations (P<0.05) between BRAF(V600E) and a higher tumor-node-metastasis staging (III/IV), and between miR-21* over-expression and lymph node metastasis.
  
  
  CONCLUSIONS
  We identified two miRNAs that are differentially expressed in PTC tissues with BRAF(V600E) and revealed their associations with clinicopathological features. These findings may lead to the development of a potential diagnostic biomarker or prognostic indicator of PTC.
authors: Department of Vascular and Thyroid Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors: Yongbo
authors: Y
authors: Huang
authors: Denghui
authors: D
authors: Liao
authors: Lingxiao
authors: L
authors: Pan
authors: Runyi
authors: R
authors: Ye
authors: Xiaoxi
authors: X
authors: Li
authors: Shenming
authors: S
authors: Wang
authors: Caisheng
authors: C
authors: Ye
authors: Liuhua
authors: L
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf