Gene expression profiling of papillary thyroid carcinoma identifies transcripts correlated with BRAF mutational status and lymph node metastasis

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dc.contributor.author Oler, Gisele [UNIFESP]
dc.contributor.author Camacho, Cleber P. [UNIFESP]
dc.contributor.author Hojaij, Flavio C. [UNIFESP]
dc.contributor.author Michaluart, Pedro
dc.contributor.author Riggins, Gregory J.
dc.contributor.author Cerutti, Janete M. [UNIFESP]
dc.date.accessioned 2016-01-24T13:51:34Z
dc.date.available 2016-01-24T13:51:34Z
dc.date.issued 2008-08-01
dc.identifier http://dx.doi.org/10.1158/1078-0432.CCR-07-4372
dc.identifier.citation Clinical Cancer Research. Philadelphia: Amer Assoc Cancer Research, v. 14, n. 15, p. 4735-4742, 2008.
dc.identifier.issn 1078-0432
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/30812
dc.description.abstract Purpose: To identify papillary thyroid carcinoma (PTC)-associated transcripts, we compared the gene expression profiles of three Serial Analysis of Gene Expression libraries generated from thyroid tumors and a normal thyroid tissue.Experimental Design: Selected transcripts were validated in a panel of 57 thyroid tumors using quantitative PCR (qPCR). An independent set of 71 paraffin-embedded sections was used for validation using immunohistochemical analysis. To determine if PTC-associated gene expression could predict lymph node involvement, a separate cohort of 130 primary PTC (54 metastatic and 76 nonmetastatic) was investigated. the BRAF(V600E) mutational status was compared with qPCR data to identify genes that might be regulated by abnormal BRAF/MEK/extracellular signal-regulated kinase signaling.Results: We identified and validated new PTC-associated transcripts. Three genes (CST6, CXCL14, and DHRS3) are strongly associated with PTC. Immunohistochemical analysis of CXCL14 confirmed the qPCR data and showed protein expression in PTC epithelial cells. We also observed that CST6, CXCL14, DHRS3, and SPP1 were associated with PTC lymph node metastasis, with CST6, CXCL14, and SPP1 being positively correlated with metastasis and DHRS3 being negatively correlated. Finally, we found a strong correlation between CST6 and CXCL14 expression and BRAF(V600E) mutational status, suggesting that these genes may be induced subsequently to BRAF activation and therefore may be downstream in the BRAF/MEK/extracellular signal-regulated kinase signaling pathway.Conclusion: CST6, CXCL14, DHRS3, and SPP1 may play a role in PTC pathogenesis and progression and are possible molecular targets for FTC therapy. en
dc.format.extent 4735-4742
dc.language.iso eng
dc.publisher Amer Assoc Cancer Research
dc.relation.ispartof Clinical Cancer Research
dc.rights Acesso aberto
dc.title Gene expression profiling of papillary thyroid carcinoma identifies transcripts correlated with BRAF mutational status and lymph node metastasis en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Johns Hopkins Univ
dc.description.affiliation Universidade Federal de São Paulo, Genet Bases Thyroid Tumor Lab, Div Genet, BR-04039032 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Div Endocrinol, BR-04039032 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Div Head & Neck Surg, BR-04039032 São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Sch Med, Dept Surg, São Paulo, Brazil
dc.description.affiliation Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Genet Bases Thyroid Tumor Lab, Div Genet, BR-04039032 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Div Endocrinol, BR-04039032 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Div Head & Neck Surg, BR-04039032 São Paulo, Brazil
dc.identifier.doi 10.1158/1078-0432.CCR-07-4372
dc.description.source Web of Science
dc.identifier.wos WOS:000258217200010



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