title: Genome-wide expression analysis suggests a crucial role of dysregulation of matrix metalloproteinases pathway in undifferentiated thyroid carcinoma.
abstract: BACKGROUND
  Thyroid cancer (TC) is the most common malignant cancer of the Endocrine System. Histologically, there are three main subtypes of TC: follicular, papillary and anaplastic. Diagnosing a thyroid tumor subtype with a high level of accuracy and confidence is still a difficult task because genetic, molecular and cellular mechanisms underlying the transition from differentiated to undifferentiated thyroid tumors are not well understood. A genome-wide analysis of these three subtypes of thyroid carcinoma was carried out in order to identify significant differences in expression levels as well as enriched pathways for non-shared molecular and cellular features between subtypes.
  
  
  RESULTS
  Inhibition of matrix metalloproteinases pathway is a major event involved in thyroid cancer progression and its dysregulation may result crucial for invasiveness, migration and metastasis. This pathway is drastically altered in ATC while in FTC and PTC, the most important pathways are related to DNA-repair activation or cell to cell signaling events.
  
  
  CONCLUSIONS
  A progression from FTC to PTC and then to ATC was detected and validated on two independent datasets. Moreover, PTX3, COLEC12 and PDGFRA genes were found as possible candidates for biomarkers of ATC while GPR110 could be tested to distinguish PTC over other tumor subtypes. The genome-wide analysis emphasizes the preponderance of pathway-dysregulation mechanisms over simple gene-malfunction as the main mechanism involved in the development of a cancer phenotype.
authors.affiliation: National Institute of Genomic Medicine, Periférico Sur 4809, Arenal Tepepan, TlalpanMéxico City, 14610, México. jespinal@inmegen.gob.mx.|Center for Sciences of Complexity (C3), UNAM, Ciudad Universitaria, México City, 01010, México. jespinal@inmegen.gob.mx.
authors.forename: Jesús
authors.initials: J
authors.lastname: Espinal-Enríquez
authors.affiliation: National Institute of Genomic Medicine, Periférico Sur 4809, Arenal Tepepan, TlalpanMéxico City, 14610, México. smunoz@grupoabraxas.com.
authors.forename: Said
authors.initials: S
authors.lastname: Muñoz-Montero
authors.affiliation: National Institute of Genomic Medicine, Periférico Sur 4809, Arenal Tepepan, TlalpanMéxico City, 14610, México. iimaz@inmegen.gob.mx.
authors.forename: Ivan
authors.initials: I
authors.lastname: Imaz-Rosshandler
authors.affiliation: National Institute of Genomic Medicine, Periférico Sur 4809, Arenal Tepepan, TlalpanMéxico City, 14610, México. ajosuehv@gmail.com.
authors.forename: Aldo
authors.initials: A
authors.lastname: Huerta-Verde
authors.affiliation: Faculty of Natural Sciences, Autonomous University of Querétaro, P.O. Box 184, Querétaro, 76230, México. Maria.C.Mejia@uv.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Mejía
authors.affiliation: National Institute of Genomic Medicine, Periférico Sur 4809, Arenal Tepepan, TlalpanMéxico City, 14610, México. ehernandez@inmegen.gob.mx.|Center for Sciences of Complexity (C3), UNAM, Ciudad Universitaria, México City, 01010, México. ehernandez@inmegen.gob.mx.
authors.forename: Enrique
authors.initials: E
authors.lastname: Hernández-Lemus
mesh_terms: D015415:Biomarkers; D002450:Cell Communication; D002470:Cell Survival / Q000235:genetics; D019295:Computational Biology; D030541:Databases, Genetic; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D060787:Neoplasm Grading; D012372:ROC Curve; D015203:Reproducibility of Results; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D020782:Matrix Metalloproteinases