03141nas a2200313   4500008004100000245013000041210006900171300001200240490000700252520169500259653011401954653003602068653016902104653009402273653012702367100002202494700002602516700001402542700001602556700003002572700001702602700001702619700002002636700001502656700001702671700001602688700001702704856010602721       2008                        eng d00aMolecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information0 aMolecular profiling related to poor prognosis in thyroid carcino  a1554-610 v273 a<p>Undifferentiated and poorly differentiated thyroid tumors are responsible for more than half of thyroid cancer patient deaths in spite of their low incidence. Conventional treatments do not obtain substantial benefits, and the lack of alternative approaches limits patient survival. Additionally, the absence of prognostic markers for well-differentiated tumors complicates patient-specific treatments and favors the progression of recurrent forms. In order to recognize the molecular basis involved in tumor dedifferentiation and identify potential markers for thyroid cancer prognosis prediction, we analysed the expression profile of 44 thyroid primary tumors with different degrees of dedifferentiation and aggressiveness using cDNA microarrays. Transcriptome comparison of dedifferentiated and well-differentiated thyroid tumors identified 1031 genes with &gt;2-fold difference in absolute values and false discovery rate of &lt;0.15. According to known molecular interaction and reaction networks, the products of these genes were mainly clustered in the MAPkinase signaling pathway, the TGF-beta signaling pathway, focal adhesion and cell motility, activation of actin polymerization and cell cycle. An exhaustive search in several databases allowed us to identify various members of the matrix metalloproteinase, melanoma antigen A and collagen gene families within the upregulated gene set. We also identified a prognosis classifier comprising just 30 transcripts with an overall accuracy of 95%. These findings may clarify the molecular mechanisms involved in thyroid tumor dedifferentiation and provide a potential prognosis predictor as well as targets for new therapies.</p>10aAdenoma/genetics/metabolism/pathology Adolescent Adult Aged Carcinoma/genetics/metabolism/pathology Carcinoma10aBiological/*genetics/metabolism10aNeoplasm/genetics/metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Thyroid Neoplasms/classification/*genetics/metabolism Tumor Markers10aNeoplastic Humans Male Middle Aged *Oligonucleotide Array Sequence Analysis Prognosis RNA10aPapillary/genetics/metabolism/pathology Cell Differentiation Female *Gene Expression Profiling *Gene Expression Regulation1 aMontero-Conde, C.1 aMartin-Campos, J., M.1 aLerma, E.1 aGimenez, G.1 aMartinez-Guitarte, J., L.1 aCombalia, N.1 aMontaner, D.1 aMatias-Guiu, X.1 aDopazo, J.1 ade Leiva, A.1 aRobledo, M.1 aMauricio, D.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17873908