title: DNA microarray and miRNA analyses reinforce the classification of follicular thyroid tumors.
abstract: BACKGROUND
  Focusing on mitochondrial function and thyroid tumorigenesis, we used an integrative approach to identify relevant biomarkers for borderline thyroid lesions.
  
  
  METHODS
  Using cDNA and microRNA (miRNA) microarrays and quantitative RT-PCR analysis (qPCR), we explored samples of various types of thyroid tumors including 25 benign follicular adenomas represented by macrofollicular variants of thyroid adenomas, 38 oncocytic variants of follicular thyroid tumors, 19 papillary thyroid carcinomas, and 10 tumors of uncertain malignant potential, together with 53 normal thyroid tissue samples.
  
  
  RESULTS
  Our transcriptomic analysis, which highlighted discrepancies between controls and tumor tissues, as well as between various tumor types, led to the identification of 13 genes, allowing discrimination between the thyroid adenomas, oncocytic variants of follicular thyroid tumors, and papillary thyroid carcinomas, whereas the tumors of uncertain malignant potential were found to overlap these classes. Five of these genes (TP53, HOXA9, RUNX1, MYD88, and CITED1), with a differential expression confirmed by qPCR analysis, are implicated in tumorigenesis, 4 in mitochondrial metabolism (MRPL14, MRPS2, MRPS28, and COX6A1), and 2 in thyroid metabolic pathways (CaMKIINalpha and TPO). The global miRNA analysis revealed 62 differential miRNAs, the expression level for 10 of these being confirmed by qPCR. The differential expression of the miRNAs was in accordance with the modulation of gene expression and the ontologies revealed by our transcriptomic analysis.
  
  
  CONCLUSIONS
  These findings reinforce the classification of follicular thyroid tumors established by the World Health Organization, and our technique offers a novel molecular approach to refine the classification of thyroid tumors of uncertain malignant potential.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U694, rue des Capucins, F-49033 Angers, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jacques
authors.forename: Delphine
authors.initials: D
authors.lastname: Guillotin
authors.forename: Jean-Fred
authors.initials: JF
authors.lastname: Fontaine
authors.forename: Brigitte
authors.initials: B
authors.lastname: Franc
authors.forename: Delphine
authors.initials: D
authors.lastname: Mirebeau-Prunier
authors.forename: Audrey
authors.initials: A
authors.lastname: Fleury
authors.forename: Yves
authors.initials: Y
authors.lastname: Malthiery
authors.forename: Frédérique
authors.initials: F
authors.lastname: Savagner
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D000236:Adenoma / Q000175:diagnosis / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism / Q000601:surgery; D002291:Carcinoma, Papillary; D016000:Cluster Analysis; D016002:Discriminant Analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D012334:RNA, Neoplasm / Q000378:metabolism*; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm